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Hira Tohru

Research Faculty of Agriculture Fundamental AgriScience Research Bioscience and ChemistryProfessor
Institute for the Promotion of Business-Regional CollaborationProfessor

Researcher basic information

■ Degree
  • Ph.D. in Agricultural Chemistry, Hokkaido University
■ URL
researchmap URL■ Various IDs
J-Global ID■ Research Keywords and Fields
Research Keyword
  • enteroendocrine cells
  • gastrointestinal hormone
  • 栄養生理学
  • 消化管生理学
  • Nutritional physiology
Research Field
  • Life Science, Food sciences, 栄養生理学
  • Life Science, Physiology
■ Educational Organization

Career

■ Career
Career
  • Apr. 2026 - Present
    Hokkaido University, Research Faculty of Agriculture, 教授
  • Apr. 2020 - Mar. 2026
    北海道大学大学院農学研究院 准教授
  • Apr. 2013 - Mar. 2020
    Hokkaido University, Graduate School of Agriculture Research Faculty of Agriculture, 講師
  • Apr. 2007 - Mar. 2013
    Hokkaido University, Graduate School of Agriculture Research Faculty of Agriculture, 助教
  • Jan. 2005 - Mar. 2007
    北海道大学大学院農学研究科(院), 助手
  • 2003 - 2004
    北海道大学大学院農学研究科 研究員
  • Nov. 2001 - Mar. 2003
    University of Manchester (UK), Visiting Research Fellow
  • 2000 - 2003
    北海道大学大学院農学研究科 日本学術振興会特別研究員
  • 1999 - 2000
    北海道科学・技術振興財団 研究員
Educational Background
  • Sep. 1999, Hokkaido University, 大学院農学研究科, 農芸化学専攻 博士後期課程修了, Japan
  • Mar. 1997, Hokkaido University, 大学院農学研究科, 農芸化学専攻 修士課程修了, Japan
  • Mar. 1995, Hokkaido University, Faculty of Agriculture, 農芸化学科 卒業, Japan
  • 鹿児島県立志布志高等学校 卒業
Committee Memberships
  • Apr. 2027 - Present
    日本アミノ酸学会, 編集幹事
  • Jun. 2026 - Present
    日本食物繊維学会, 学会誌編集委員
  • May 2024 - Present
    日本栄食・食糧学会, 国際交流委員
  • Feb. 2024 - Present
    Endocrinology, Editorial board, Society
  • Nov. 2023 - Present
    日本食物繊維学会, 理事, Society
  • Nov. 2019 - Present
    日本栄養・食糧学会, 代議員, Society
  • Sep. 2011 - Present
    日本栄養・食糧学会 北海道支部, 参与, Society
  • Apr. 2015 - Mar. 2027
    日本アミノ酸学会, 評議員, Society
  • May 2022 - May 2026
    日本栄養・食糧学会, 用語委員会
  • May 2022 - May 2026
    日本栄養・食糧学会, 学会誌編集委員
  • May 2024 - Mar. 2025
    日本農芸化学会2025年度大会, 実行委員(プログラム)
  • 2024 - 2025
    日本農芸化学会2025年度大会, 実行委員
  • Jun. 2022 - May 2024
    日本栄養・食糧学会北海道支部, 庶務幹事
  • 2022 - 2024
    日本栄養・食糧学会, 広報委員
  • Sep. 2021 - Oct. 2023
    日本食物繊維学会, 評議員, Society
  • 2022 - 2023
    第77回日本栄養・食糧学会大会, 実行委員(総務・会計責任者)
  • Jun. 2019 - May 2021
    日本農芸化学会北海道支部, 庶務幹事, Society
  • 2015 - 2016
    日本農芸化学会2016年度大会, 実行委員(総務)
  • 2013 - 2014
    第68回日本栄養・食糧学会大会, 実行委員(会計責任者)
  • 2006 - 2014
    日本栄養・食糧学会 北海道支部, 会計幹事
  • 2005
    日本農芸化学会2005年度大会, 実行員(会場)

Research activity information

■ Awards
  • Oct. 2026, 日本農芸化学会, 2026年度日本農芸化学会東北・北海道支部合同支部大会 学生優秀発表賞
    ケルセチンとその配糖体におけるin vitroにおけるGLP-1分泌とin vivoにおける血糖上昇抑制作用の検討
    近藤 杏南
  • Sep. 2026, 日本アミノ酸学会, 日本アミノ酸学会第19回学術大会優秀発表賞
    アルロースとアミノ酸の共投与による血糖上昇抑制作用の検討
    水間 志織
  • Feb. 2026, 日本農芸化学会, 2025年 B.B.B.論文賞
    Oral administration of L-lysine potently promotes glucagon-like peptide-1 secretion and lowers glycemic response in rats
    入江 明歩、比良 徹
  • Nov. 2025, 日本アミノ酸学会, 日本アミノ酸学会第19回学術大会優秀発表賞
    ラットにおいてL-リジンとカルシウムの経口投与は血糖上昇を抑制する
    入江 明歩
  • May 2024, 日本栄養・食糧学会, 第78回日本栄養・食糧学会大会 優秀発表賞
    ラットにおいて希少糖アルロースにより生じる回腸の伸展がGLP-1 分泌を促進する
    水間 志織
  • May 2024, 日本栄養・食糧学会, 第78回日本栄養・食糧学会 トピックス賞
    「ラットにおいて希少糖アルロースにより生じる回腸の伸展がGLP-1 分泌を促進する」
    水間 志織、比良 徹
  • Dec. 2023, 2023年度 日本農芸化学会北海道支部 第二回学術講演会, 学生優秀発表賞
    ラットにおけるL-リジンのGLP-1 分泌促進作⽤
    入江 明歩
  • Nov. 2023, 日本食物繊維学会, 日本食物繊維学会第28回学術集会発表賞
    アルロースによる伸展刺激を介したGLP-1分泌機構の解明
    水間 志織
  • Nov. 2022, 日本食物繊維学会, 令和4年度 日本食物繊維学会 学会賞
    ルミナコイドによる消化管ホルモン分泌促進作用
    比良 徹
  • Jul. 2021, 日本農芸化学会北海道支部, 2021年度日本農芸化学会北海道支部第1回講演会 学生優秀発表賞
    ラットにおけるカルシウムによる食欲抑制に対する食事組成の影響
    原田 和馬, Japan society
  • May 2021, 日本栄養·食糧学会, 令和3年度 日本栄養·食糧学会トピックス賞
    2-モノアシルグリセロールのCCK分泌活性評価およびその作用機構の解明
    落合 啓太、廣岡 里菜、境野 眞善、竹内 茂雄、比良 徹, Japan society
  • Dec. 2020, 日本栄養・食糧学会北海道支部, 2020年度 日本農芸化学会北海道支部/第50回 日本栄養・食糧学会北海道支部 合同学術講演会 若手奨励賞
    ラットにおける伸展刺激負荷による GLP-1 分泌応答の解析
    木村 夏織, Japan society
  • Mar. 2020, 日本農芸化学会, 日本農芸化学会 2020年度大会 優秀発表賞
    食事誘導性肥満ラットにおけるGLP-1分泌応答の増強には回腸部が寄与する
    佐野 杏莉, Japan society
  • Nov. 2019, 日本食物繊維学会, 日本食物繊維学会第 24回学術集会 発表賞
    ラットにおける D- アルロースによる GLP-1 分泌促進機構の解析
    木村夏織, Japan society
  • Nov. 2019, 日本農芸化学会北海道支部, 日本農芸化学会 北海道支部第2回講演会 学生優秀発表賞
    食事誘導性肥満ラットにおけるGLP-1の分泌応答と小腸上部および下部での違い
    佐野 杏莉, Japan society
  • Sep. 2019, 日本栄養・食糧学会北海道支部, 第49回 日本栄養・食糧学会北海道支部会 若手奨励賞
    タンパク質投与で生じる高い GLP-1 応答への DPP-4 の関与
    清水 祐希, Japan society
  • Jul. 2019, 日本農芸化学会北海道支部, 2019年度日本農芸化学会 北海道支部第1回講演会 学生優秀発表賞
    ラットへの食用油経口投与による胃排出への影響
    李 佳昕, Japan society
  • May 2018, 日本栄養・食糧学会, 第 72 回日本栄養・食糧学会大会 トピックス演題
    Zein加水分解物による小腸部位別でのGLP-1分泌応答
    清水 祐希;比良 徹;原 博, Japan society
  • Nov. 2017, 第24回日本未病システム学会学術総会 優秀演題賞
    ケルセチン配糖体の反復投与は糖負荷後のラットGLP-1分泌能を増強する
    長瀬 僚介, Japan society
  • Jul. 2017, 日本農芸化学会北海道支部, 平成29年度日本農芸化学会北海道支部第1回講演会学生優秀発表賞
    The role of endogenous GLP-1 against the development of glucose intolerance in rats fed a high fat and high sucrose diet
    Jukkrapong Pinyo, Japan society
  • May 2017, 日本栄養・食糧学会, 第 71 回日本栄養・食糧学会大会 学生優秀発表賞
    肥満誘導食摂取ラットにおける食事刺激に対するGLP-1分泌応答の解析
    柳原 くるみ, Japan society
  • Nov. 2016, 日本食物繊維学会, 日本食物繊維学会 第21回学術集会 発表賞
    D-プシコースによる GLP-1 分泌促進作用における糖輸送担体の関与
    早川 真輝, Japan society
  • May 2016, 日本栄養・食糧学会, 第70回日本栄養・食糧学会大会 学生優秀発表賞
    D-プシコースの経口投与はラットにおいてGLP-1分泌を促進する
    早川 真輝, Japan society
  • Sep. 2014, The XXVIIth International Conference on Polyphenols (ICP 2014) and 8th Tannin Conference, The XXVIIth International Conference on Polyphenols (ICP 2014) and 8th Tannin Conference Poster Award
    A non-digestible saccharide, fructooligosaccharide, increases the promotive effect of a flavonoid, α-glucosyl-isoquercetin, on glucagon-like peptide 1 (GLP-1) secretion in rat intestine and enteroendocrine cells.
    Phuwamongkolwiwat P, International society
  • Nov. 2013, 日本アミノ酸学会, 2013年度日本アミノ酸学会 科学・技術賞
    比良 徹, Japan society
  • Nov. 2012, 日本食物繊維学会 17回学術集会, 日本食物繊維学会 17回学術集会 発表賞
    難消化性デキストリンの単回及び長期摂取はラットのGLP-1分泌を促進する
    池江 明日香, Japan society
  • Sep. 2012, The 25th Anniversary of the Discovery of GLP-1 symposium, Young Investigator Abstract Competition Honorable Mention
    HIRA Tohru, International society
  • May 2012, 日本栄養・食糧学会, 平成24年度日本栄養・食糧学会奨励賞
    比良 徹, Japan society
  • Nov. 2011, 2011 The International Conference on Food Factors, 2011 The International Conference on Food Factors, Travel Award
    Fructooligosaccharides enhances beneficial effects of a flavonoid, quercetin-3-β-glucoside, on insulin sensitivity in rats.
    Phuwamongkolwiwat P, International society
  • Nov. 2011, 日本食物繊維学会 16 回学術集会, 日本食物繊維学会 16 回学術集会 発表賞
    トウモロコシたんぱく質 Zein の加水分解物による血糖上昇抑制への GLP-1 の関与
    樋口 謹行
  • Sep. 2010, The 18th International Symposium on Regulatory Peptides, The 18th International Symposium on Regulatory Peptides, Poster Award
    Calcium-sensing receptor is a sensor for dietary peptides to stimulate cholecystokinin secretion in the enteroendocrine cell line STC-1
    S. Nakajima
  • Sep. 2010, 日本アミノ酸学会, 日本アミノ酸学会第4回学術大会 ポスター賞
    ラットにおけるCalcium-sensing receptorアゴニストによる血糖上昇抑制作用とその作用機構
    村松 茉耶
  • Nov. 2008, 日本食物繊維学会, 第13回日本食物繊維学会学術集会 奨励賞
    トウモロコシの難消化性たんぱく質Zeinの加水分解物によるラットにおける Glucagon-like peptide-1分泌機構
    持田 泰佑
■ Papers
  • Improved measurement of GLP-1 concentrations in mouse plasma by ex vivo inhibition of neprilysin.
    Chikayuki Funabashi; Tohru Hira
    Biochemical and biophysical research communications, 839, 154721, 154721, 09 Oct. 2026, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Accurate measurement of plasma glucagon-like peptide-1 (GLP-1) in mice is hindered by its rapid degradation by dipeptidyl peptidase-4 (DPP-4) and neprilysin (NEP). In vivo administration of these inhibitors can stabilize plasma GLP-1. However, GLP-1-mediated physiological functions, such as enhancing insulin secretion and suppressing gastric emptying, can be artificially altered by these inhibitors. Here, we aimed to establish a simple and reliable ex vivo inhibition method by adding the NEP inhibitor, sacubitrilat, to collection tubes. The efficacy of sacubitrilat was validated through an in vitro GLP-1 degradation assay. The ex vivo method was then evaluated during meal and glucose tolerance tests for measurement of plasma GLP-1, and compared with an in vivo inhibition method, with plasma glucose, insulin, and gastric emptying measured in parallel. In the in vitro assay, sacubitrilat addition effectively prevented GLP-1 degradation. In meal and oral glucose tolerance tests, ex vivo sacubitrilat addition yielded markedly higher plasma GLP-1 concentrations compared to standard inhibitor cocktails containing DPP-4 inhibitor, enabling clear detection of nutrient-induced GLP-1 peak. This ex vivo approach did not influence plasma glucose, insulin, and gastric emptying, thus preserving the physiological integrity of the metabolic response. In contrast to the ex vivo inhibition method, the in vivo inhibition method yielded higher GLP-1 concentrations accompanied by lowered glucose, enhanced insulin, and reduced gastric emptying. Our findings demonstrate that the addition of the NEP inhibitor to tubes is an effective strategy for the precise measurement of GLP-1 secretory dynamics, particularly in the measurement of multiple physiological parameters.
  • 抗肥満・抗糖尿病ホルモンGLP-1の新たな分泌メカニズム 腸の伸展を介したGLP-1分泌
    水間 志織; 比良 徹
    化学と生物, 64, 3, 127, 128, (公社)日本農芸化学会, May 2026, [Peer-reviewed], [Last author, Corresponding author]
    Japanese
  • Oral administration of l-lysine potently promotes GLP-1 secretion and lowers glycemic response in rats.
    Akiho Irie; Tohru Hira
    Bioscience, biotechnology, and biochemistry, 03 Sep. 2025, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that suppresses postprandial glycemia and appetite. GLP-1 secretion is promoted by various nutrients; however, studies on the effects of orally administered amino acids on GLP-1 secretion are limited. This study investigated the acute effects of l-lysine (Lys) on GLP-1 secretion in vivo and explored the underlying mechanisms. In male Sprague-Dawley rats, oral administration Lys, but not l-Alanine (Ala), elevated plasma GLP-1 concentrations, with comparable to or higher potency compared to other amino acids known to stimulate GLP-1 secretion. Duodenal administration of CaSR antagonist attenuated Lys-induced GLP-1 secretion. Oral co-administration of Lys and calcium potently promoted GLP-1 secretion and lowered glycemia under an oral glucose tolerance test. These findings demonstrate that Lys potently induces GLP-1 secretion in vivo, and the combination of Lys and calcium has translational potential as potent GLP-1 releasing strategy for the management of blood glucose levels.
  • Glucagon-like peptide-1 responses to carbohydrate, fat and protein in rats during the development of diet-induced obesity and the role of the distal small intestine.
    Anri Sano; Satomi Tanaka; Kurumi Yanagihara; Yasuko Sakihama; Tohru Hira
    The British journal of nutrition, 1, 9, 28 Jul. 2025, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, The secretion of glucagon-like peptide-1 (GLP-1) is stimulated by luminal nutrients after meal ingestion. Diet-induced obesity (DIO) may affect nutrient-induced GLP-1 secretion in humans and rodent models. We previously demonstrated that mixed meal-induced GLP-1 secretion is enhanced in rats with DIO compared with normal rats. However, it is unclear to which nutrient the GLP-1 secretion is adaptively enhanced or reduced during the development of DIO. The present study investigated the effect of obesity on the GLP-1 secretion to individual nutrients and further on GLP-1 secretory functions of the proximal and distal small intestine in rats. Male Sprague-Dawley rats were fed a control diet or a high-fat diet with sucrose solution (HFS) for 4–5 weeks. GLP-1 responses to a single oral administration of a liquid diet, dextrin, soyabean oil or whey protein were examined after 4 weeks of dietary intervention. In addition, a liquid diet was administered to the proximal or distal small intestine of anaesthetised rats (control or HFS), and GLP-1 levels in the portal vein plasma were measured. In HFS-fed rats, GLP-1 secretion to dextrin, soyabean oil and whey protein slightly increased compared with those in normal rats. Furthermore, the GLP-1 response to liquid diet administration into the lumen was greater in the distal, but not proximal, small intestine of HFS-fed rats than that in control rats. In rats with DIO, GLP-1 secretion increased, regardless of the type of nutrient. Furthermore, the distal small intestine is responsible for adaptive enhancement of the GLP-1 secretion.
  • Abilities of Rare Sugar Members to Release Glucagon-like Peptide-1 and Suppress Food Intake in Mice.
    Yuta Masuda; Kento Ohbayashi; Kengo Iba; Rika Kitano; Tomonori Kimura; Takako Yamada; Tohru Hira; Toshihiko Yada; Yusaku Iwasaki
    Nutrients, 17, 7, 31 Mar. 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Background/Objectives: Rare sugars, which naturally exist in small quantities, have gained attention as next-generation functional sugars due to their sweetness and low calorie content. Some of them have already been commercialized. Rare sugar-containing syrups, produced through alkaline isomerization of high-fructose corn syrup, are effective in preventing obesity and type 2 diabetes. However, the mechanisms underlying these effects remain incompletely understood. Recently, D-allulose has been found to improve hyperphagic obesity by stimulating the secretion of the intestinal hormone glucagon-like peptide-1 (GLP-1). The present study aimed to determine the comparative effects of aldohexoses (D-glucose, D-allose) and ketohexoses (D-fructose, D-allulose, D-tagatose, D-sorbose) on GLP-1 secretion and food intake in male mice. Method and Results: Single peroral administration of four ketohexoses at 1 and 3 g/kg, but not aldohexoses at 1 and 3 g/kg, significantly increased plasma GLP-1 concentrations with comparable efficacy. Moreover, these ketohexoses at 1 g/kg suppressed food intake in the short term, an effect blunted by GLP-1 receptor antagonism. In contrast, zero-calorie D-allose at 3 g/kg suppressed feeding without raising plasma GLP-1 levels. Conclusions: These results demonstrate that D-allulose, D-tagatose, and D-sorbose, which are low-calorie rare sugars classified as ketohexoses, suppress food intake through promoting GLP-1 secretion, showing their potential to prevent and/or ameliorate type 2 diabetes, obesity and related diseases.
  • Intestinal Distension Induced by Luminal D-allulose Promotes GLP-1 Secretion in Male Rats.
    Shiori Mizuma; Masaki Hayakawa; Tohru Hira
    Endocrinology, 166, 2, 06 Jan. 2025, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, The secretion of glucagon-like peptide-1 (GLP-1) is promoted by various nutrients, and glucose and fructose stimulate GLP-1 secretion via intracellular metabolism. D-allulose (allulose), a nonmetabolizable epimer of D-fructose, is also effective in stimulating GLP-1 secretion, although its underlying mechanism remains unclear. We previously observed intestinal distension after the oral administration of allulose, accompanied by increased GLP-1 secretion in rats, possibly because of the low or slow absorbability of allulose. In this study, we sought to determine whether intestinal distension caused by allulose and other factors gives rise to GLP-1 secretion in rats. We found that the oral coadministration of carbonated water enhanced allulose-induced GLP-1 secretion. Polyethylene glycol 1000 and D-mannitol, which are water-soluble and poorly absorbable, stimulated GLP-1 secretion. However, cellulose (insoluble), and tetra ethylene glycol (water-soluble and absorbable) did not. The secretion of GLP-1 increased as the absolute amount of allulose increased, independent of the concentration. The extent of the GLP-1 secretory response was positively correlated with the intestinal content volume and diameter after allulose administration. Furthermore, the intraileal administration of air expanded the intestine-induced secretion of GLP-1. Our results demonstrate that allulose promotes GLP-1 secretion, at least in part, via intestinal distension as a novel GLP-1 secretory mechanism. Physical stimulation may also contribute to postprandial GLP-1 secretion.
  • Differential Regulation of Cholecystokinin Production by Synthetic and Natural Glucocorticoids in Enteroendocrine Cells.
    Shingo Nakajima; Shoko Tsuchimine; Tohru Hira; Hiroshi Kunugi
    Journal of nutritional science and vitaminology, 71, 5, 411, 420, 2025, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Chronic stress often causes abnormal eating behavior and metabolism due at least in part to the activation of hypothalamic-pituitary-adrenal (HPA) axis resulting in increases glucocorticoids secretion. Cholecystokinin (CCK) is an anorexic gut hormone secreted from enteroendocrine I cells and controls digestion through the gastric emptying and digestive enzyme secretion. In the present study, we highlighted the function of glucocorticoids in CCK-producing cells with enteroendocrine model cell lines and male Wistar rats. We found that glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are expressed in STC-1 cells known as an I cell model line. Synthetic (dexamethasone; DEX) and endogenous (corticosterone; CORT) glucocorticoids reduced CCK transcription in STC-1 cells. Depolarization-induced CCK secretion was attenuated by both glucocorticoids, whereas dietary peptide-induced CCK secretion was enhanced by acute CORT treatment. DEX and CORT treatments weakened phosphorylated signaling pathway for CCK transcription in an agonist-specific manner. Daily single injection of DEX but not CORT for 4 d decreased Cck mRNA in the upper small intestine with altered metabolism and gut glucocorticoid sensitivity in male Wistar rats. These findings provide a new insight to reveal stress-induced abnormal nutrient and metabolic status in relation to gastrointestinal dysfunctions.
  • Amino acid transport dynamics in the jejunum and ileum in rats: a regional and time-course analysis.
    Kojiro Katsura; Tohru Hira
    The British journal of nutrition, 132, 10, 1278, 1288, 28 Nov. 2024, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Postprandially, amino acids and di/tripeptides are thought to be primarily absorbed in the proximal small intestine. However, there have been no in vivo demonstrations of regional differences in amino acid transport dynamics between the proximal and distal small intestines. We monitored plasma amino acid responses in the jejunal and ileal mesenteric veins of rats after oral administration of a diet or an amino acid mixture (Expt 1) and in the portal vein after direct administration of the amino acid mixture into the lumen of the jejunum or ileum (Expt 2). In Expt 1, the total and some amino acid concentrations in the jejunal mesenteric vein were slightly higher than those in the ileal mesenteric vein after oral administration of the amino acid mixture, suggesting that the ileum actively transports luminal amino acids to the basolateral side, comparable to the jejunum. In Expt 2, portal amino acid concentrations were elevated to a greater extent after direct administration of the amino acid mixture into the ileal lumen than into the jejunal lumen. These results demonstrate regional differences in amino acid transport dynamics in vivo and suggest that the ileum has a higher capacity for transporting amino acids than the jejunum. Our findings highlight the importance of the ileum in postprandial amino acid absorption and metabolism.
  • Targeting intestinal neprilysin to ameliorate glucose homeostasis through insulinotropic effect.
    Shiori Mizuma; Tohru Hira
    Endocrinology, 27 Sep. 2024, [Peer-reviewed], [Invited], [Last author, Corresponding author], [International Magazine]
    English
  • Effect of Single Oral Coingestion of GABA and Malic Acid on Postprandial GLP-1, Glucose, and Insulin Responses in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.
    Hiroki Noguchi; Takeshi Ikenaga; Shota Ueno; Chieko Kohashi; Yasuhiro Matsumura; Yusuke Kakumoto; Noriyuki Kohda; Hiroshi Hara; Tohru Hira
    Molecular nutrition & food research, 68, 7, e2300610, Apr. 2024, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, SCOPE: This study examines whether coingestion of γ-aminobutyric acid (GABA) and malic acid (MA) before meals enhances glucagon-like peptide-1 (GLP-1) secretion, and which affects subsequent insulin and glycemic responses in humans. METHODS AND RESULTS: Initially, a murine enteroendocrine STC-1 cell line is used to verify coadministration of GABA and MA synergistically induces GLP-1 secretion. Next, 22 healthy adults are given water (50 mL) containing 400 mg GABA and 400 mg MA (Test), or only 400 mg citric acid (CA) (Placebo) 20 min before meal tolerance test (MTT). Interval blood samples are taken postprandially over 180 min to determine GLP-1, insulin, and glucose responses. By comparison to preload of Placebo, preload of Test significantly increases plasma GLP-1 (total/active) levels (incremental area under the curve by 1.2- and 1.6-fold), respectively. However, there are no significant differences in postprandial blood glucose and insulin. CONCLUSION: Coingestion of GABA and MA before meals enhances postprandial GLP-1 secretion. Future studies should explore optimal dosage regimens to find the efficacy of the mixture on insulin and glycemic response.
  • 食品タンパク質・ペプチドによるGLP-1分泌促進とそれによる血糖上昇抑制、体温上昇作用
    比良 徹
    日本栄養・食糧学会誌, 77, 1, Feb. 2024, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
  • Tunable structure of chimeric isomaltomegalosaccharides with double α-(1 → 4)-glucosyl chains enhances the solubility of water-insoluble bioactive compounds
    Weeranuch Lang; Takayoshi Tagami; Yuya Kumagai; Seiya Tanaka; Hye-Jin Kang; Masayuki Okuyama; Wataru Saburi; Haruhide Mori; Tohru Hira; Chaehun Lee; Takuya Isono; Toshifumi Satoh; Hiroshi Hara; Takayuki Kurokawa; Nobuo Sakairi; Yoshiaki Yuguchi; Atsuo Kimura
    Carbohydrate Polymers, 319, 121185, 121185, Elsevier BV, Nov. 2023, [Peer-reviewed]
    Scientific journal
  • Synergistic enhancement of glucagon-like peptide-1 release by γ-aminobutyric acid and L-phenylalanine in enteroendocrine cells - searching active ingredients in a water extract of Corn Zein protein.
    Hiroki Noguchi; Noriyuki Kohda; Hiroshi Hara; Tohru Hira
    Bioscience, biotechnology, and biochemistry, 04 Sep. 2023, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, This study investigated the glucagon-like peptide-1 (GLP-1)-releasing activity of an aqueous extract (ZeinS) from corn zein protein, and aimed to identify the active compounds responsible for this activity. GLP-1-releasing activity was evaluated using a murine enteroendocrine cell line (GLUTag). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed on purified fractions of ZeinS to identify active molecules. ZeinS stimulated more GLP-1 secretion from GLUTag cells compared to zein hydrolysate. Fractions displaying biological activity were determined by solid phase extraction and high-performance liquid chromatography (HPLC) fractionation. Subsequent LC-MS/MS analysis identified several amino acids in the active fractions of ZeinS. In particular, γ-aminobutyric acid (GABA) exhibited significant GLP-1 releasing activity both alone and synergistically with L-phenylalanine (Phe). Moreover, ZeinS-induced GLP-1 secretion was attenuated by antagonists for the GABA receptor and calcium sensing receptor. These results demonstrate that GABA and Phe identified in ZeinS synergistically stimulate GLP-1 secretion in enteroendocrine cells.
  • Trp-Tyr is a dipeptide structure that potently stimulates GLP-1 secretion in a murine enteroendocrine cell model, identified by comprehensive analysis.
    Hayate Taguchi; Kana Murai; Tohru Hira
    Biochemical and biophysical research communications, 661, 28, 33, 18 Jun. 2023, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Dietary peptides potently stimulate glucagon-like peptide-1 (GLP-1) secretion, however, the underlying molecular mechanisms, such as structure-activity relationships and sensing mechanisms are only partly elucidated. In this study, we used a dipeptide library to identify dipeptides that potently stimulate GLP-1 release and to clarify the underlying structure-activity relationship. Murine enteroendocrine GLUTag cells were exposed to 339 dipeptides for 60 min, and the concentration of GLP-1 released into the supernatant was measured. Subsequently, selected dipeptides were examined for their reproducibility and dose responsiveness. In addition, we investigated the role of constituent amino acids in the secretion of GLP-1, and whether tripeptides containing the active dipeptide structures maintained their activity. In a concentration range of 1-5 mg/mL, twelve dipeptides had reproducible and concentration-dependent GLP-1-releasing activity. Among them, nine dipeptides (FY, KF, NI, PM, QL, QY, WF, WN, WY) were novel, with WY exhibiting the most potent activity. The reverse sequences and most free amino acids did not induce GLP-1 secretion, indicating that GLP-1-producing cells recognize the structure of each peptide to induce GLP-1 secretion. However, no apparent similarities were found between the active peptides. A comparison between the six tripeptides composed of F, W, and Y revealed the further potent tripeptides FWY and WYF, than WY. In the present study, a comprehensive analysis revealed nine novel dipeptides with high potential to stimulate GLP-1 secretion. Furthermore, the results indicate that 'WY' is a specific dipeptide sequence that potently stimulates GLP-1 secretion.
  • Glucagon-like peptide-1 is involved in the thermic effects of dietary proteins in male rodents.
    Keita Ochiai; Asuka Muto; Bong Soo Seok; Yuta Doi; Yusaku Iwasaki; Yuko Okamatsu-Ogura; Daniel J Drucker; Tohru Hira
    Endocrinology, 04 May 2023, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Protein intake potently increases body temperature and energy expenditure, but the underlying mechanism thereof remains incompletely understood. Simultaneously, protein intake potently stimulates glucagon-like peptide-1 (GLP-1) secretion. Here, we examined the involvement of GLP-1 in the thermic effects of dietary proteins in rodents by measuring rectal temperature and energy expenditure and modulating GLP-1 signaling. Rectal temperature of rats or mice fasted for 4 or 5 h were measured using a thermocouple thermometer before and after an oral administration of nutrients. Oxygen consumption after oral protein administration was also measured in rats. Rectal temperature measurements in rats confirmed an increase in core body temperature after refeeding, and the thermic effect of the oral administration of protein was greater than that of a representative carbohydrate or lipid. Among the five dietary proteins examined (casein, whey, rice, egg, and soy), soy protein had the highest thermic effect. The thermic effect of soy protein was also demonstrated by increased oxygen consumption. Studies using a nonselective β-adrenergic receptor antagonist and thermal camera suggested that brown adipose tissue did not contribute to soy protein-induced increase in rectal temperature. Furthermore, the thermic effect of soy protein was completely abolished by antagonism and knockout of GLP-1 receptor, yet potentiated via augmentation of intact GLP-1 levels through inhibition of dipeptidyl peptidase-4 activity. These results indicate that GLP-1 signaling is essential for the thermic effects of dietary proteins in rats and mice, and extend the metabolic actions of GLP-1 ensuing from nutrient ingestion to encompass the thermic response to ingested protein.
  • Formulation and evaluation of a novel megalomeric microemulsion from tamarind seed xyloglucan-megalosaccharides for improved high-dose quercetin delivery
    Weeranuch Lang; Debashish Mondol; Aphichat Trakooncharoenvit; Takayoshi Tagami; Masayuki Okuyama; Tohru Hira; Nobuo Sakairi; Atsuo Kimura
    Food Hydrocolloids, 137, Apr. 2023, [Peer-reviewed]
    Scientific journal
  • Research on Luminacoids-Indeced Gastrointestinal Hormone Secretion
    比良徹
    ルミナコイド研究, 27, 1, 1, 7, 2023, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
  • Direct visualization of glucagon-like peptide-1 secretion by fluorescent fusion proteins.
    Atsushi Tsuzuki; Yoichiro Fujioka; Aiko Yoshida; Sayaka Kashiwagi; Maho Amano; Tohru Hira; Akinobu Nakamura; Hideaki Miyoshi; Tatsuya Atsumi; Yusuke Ohba
    Journal of diabetes investigation, 13, 7, 1134, 1139, 04 Apr. 2022, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Live-cell imaging with fluorescent proteins (FPs) is a powerful tool for investigating the exocytosis processes of hormones. However, the secretion process of glucagon-like peptide-1 (GLP-1) has not been visualized by FPs, which might be because tagging FPs inhibits GLP-1 synthesis through the post-translational processing from proglucagon. Here, we have developed FP-tagged GLP-1 by inserting FPs into the middle of GLP-1 and adding the proglucagon signal peptide. Confocal imaging confirmed that GLP-1 fused to FPs with high folding efficiency showed granular structure, in which secretory vesicle markers colocalized. The fluorescence intensity of FP in the culture supernatant from cells treated with KCl or forskolin was significantly increased compared with those from untreated cells. Furthermore, FP-tagged GLP-1 enables direct visualization of stimulation-dependent exocytosis of GLP-1 at a single granule resolution with total internal reflection fluorescence microscopy. FP-tagged GLP-1 might facilitate the screening of GLP-1 secretagogues and the discovery of new antidiabetic drugs.
  • 2-Arachidonoyl glycerol suppresses gastric emptying via the cannabinoid receptor 1-cholecystokinin signaling pathway in mice.
    Keita Ochiai; Rina Hirooka; Masayoshi Sakaino; Shigeo Takeuchi; Tohru Hira
    Lipids, 10 Mar. 2022, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, 2-Monoacylglycerol (2-MAG) is one of the digestion products of dietary lipids. We recently demonstrated that a 2-MAG, 2-arachidonoyl glycerol (2-AG) potently stimulated cholecystokinin (CCK) secretion via cannabinoid receptor 1 (CB1) in a murine CCK-producing cell line, STC-1. CCK plays a crucial role in suppressing postprandial gastric emptying. To examine the effect of 2-AG on gastric emptying, we performed acetaminophen and phenol red recovery tests under oral or intraperitoneal administration of 2-AG in mice. Orally administered 2-AG (25 mg/kg) suppressed the gastric emptying rate in mice, as determined by the acetaminophen absorption test and phenol red recovery test. Intraperitoneal administration of a cholecystokinin A receptor antagonist (0.5 mg/kg) attenuated the gastric inhibitory emptying effect. In addition, both oral (10 mg/kg) and intraperitoneal (0.5 mg/kg) administration of a CB1 antagonist counteracted the 2-AG-induced gastric inhibitory effect. Furthermore, intraperitoneal 2-AG (25 mg/kg) suppressed gastric emptying. These results indicate that 2-AG exhibits an inhibitory effect on gastric emptying in mice, possibly mediated by stimulating both CCK secretion via CB1 expressed in CCK-producing cells and acting on CB1 expressed in the peripheral nerves. Our findings provide novel insights into the 2-MAG-sensing mechanism in enteroendocrine cells and the physiological role of 2-MAG.
  • Identification of G protein-coupled receptor 55 (GPR55) as a target of curcumin.
    Naoki Harada; Mai Okuyama; Yoshiaki Teraoka; Yumi Arahori; Yoh Shinmori; Hiroko Horiuchi; Paula B Luis; Akil I Joseph; Tomoya Kitakaze; Shigenobu Matsumura; Tohru Hira; Norio Yamamoto; Takashi Iuni; Naoki Goshima; Claus Schneider; Hiroshi Inui; Ryoichi Yamaji
    NPJ science of food, 6, 1, 4, 4, 14 Jan. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The identification of molecular targets of bioactive food components is important to understand the mechanistic aspect of their physiological functions. Here, we have developed a screening system that enables us to determine the activation of G protein-coupled receptors (GPCRs) by food components and have identified GPR55 as a target for curcumin. Curcumin activated GPR55 and induced serum-response element- and serum-response factor-mediated transcription, which were inhibited by Rho kinase and GPR55 antagonists. Both the methoxy group and the heptadienone moiety of curcumin were required for GPR55 activation. The F1905.47 residue of GPR55 was important for the interaction with curcumin. The curcumin-induced secretion of glucagon-like peptide-1 in GLUTag cells was inhibited by a GPR55 antagonist. These results indicate that expression screening is a useful system to identify GPCRs as targets of food components and strongly suggest that curcumin activates GPR55 as an agonist, which is involved in the physiological function of curcumin.
  • Enteroendocrine Systems That Sense Nutrients in the Gut and Control the Body
    Tohru Hira
    Journal of Nutritional Science and Vitaminology, 68, S5, S7, 2022, [Invited], [Lead author, Last author, Corresponding author]
    Scientific journal
  • GLP-1 Responses to Oral Administration of a Dietary Peptide in Rats Fed Resistant Maltodextrin or Fructooligosaccharides
    比良徹; 池江明日香; 岸本由香; 原博
    ルミナコイド研究, 26, 1, 1, 8, 2022, [Peer-reviewed], [Lead author, Corresponding author]
    Scientific journal
  • 2‐Arachidonoyl glycerol potently induces cholecystokinin secretion in murine enteroendocrine STC ‐1 cells via cannabinoid receptor CB1
    Keita Ochiai; Rina Hirooka; Masayoshi Sakaino; Shigeo Takeuchi; Tohru Hira
    Lipids, Wiley, 17 Sep. 2021, [Peer-reviewed], [Last author, Corresponding author]
    Scientific journal
  • Diet-induced obesity enhances postprandial glucagon-like peptide-1 secretion in Wistar rats, but not in diabetic Goto-Kakizaki rats.
    Jukkrapong Pinyo; Hiroshi Hara; Tohru Hira
    The British journal of nutrition, 126, 4, 518, 530, 28 Aug. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Glucagon-like peptide-1 (GLP-1) is postprandially secreted from enteroendocrine L-cells and enhances insulin secretion. Currently, it is still controversial whether postprandial GLP-1 responses are altered in obesity and diabetes. To address the issue and to find out possible factors related, we compared postprandial GLP-1 responses in normal rats and in diabetic rats chronically fed an obesogenic diet. Male Wistar rats and diabetic Goto-Kakizaki (GK) rats were fed either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose) diet for 26 weeks. Meal tolerance tests were performed for monitoring postprandial responses after a liquid diet administration (62·76 kJ/kg body weight) every 4 or 8 weeks. Postprandial glucose, GLP-1 and insulin responses in Wistar rats fed the HFS diet (WH) were higher than Wistar rats fed the control diet (WC). Although GK rats fed the HFS diet (GH) had higher glycaemic responses than GK rats fed the control diet (GC), these groups had similar postprandial GLP-1 and insulin responses throughout the study. Jejunal and ileal GLP-1 contents were increased by the HFS diet only in Wistar rats. Furthermore, mRNA expression levels of fatty acid receptors (Ffar1) in the jejunum were mildly (P = 0·053) increased by the HFS diet in Wistar rats, but not in GK rats. These results demonstrate that postprandial GLP-1 responses are enhanced under an obesogenic status in normal rats, but not in diabetic rats. Failure of adaptive enhancement of GLP-1 response in GK rats could be partly responsible for the development of glucose intolerance., 32209234;32209238
  • Improvement of Glucose Tolerance by Food Factors Having Glucagon-Like Peptide-1 Releasing Activity.
    Tohru Hira; Aphichat Trakooncharoenvit; Hayate Taguchi; Hiroshi Hara
    International journal of molecular sciences, 22, 12, 21 Jun. 2021, [Peer-reviewed], [Invited], [Lead author, Corresponding author], [International Magazine]
    English, Scientific journal, Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone released from enteroendocrine L cells in response to meal ingestion. GLP-1 receptor agonists and GLP-1 enhancers have been clinically employed to treat diabetes owing to their glucose-dependent insulin-releasing activity. The release of GLP-1 is primarily stimulated by macronutrients such as glucose and fatty acids, which are nutritionally indispensable; however, excessive intake of sugar and fat is responsible for the development of obesity and diabetes. Therefore, GLP-1 releasing food factors, such as dietary peptides and non-nutrients, are deemed desirable for improving glucose tolerance. Human and animal studies have revealed that dietary proteins/peptides have a potent effect on stimulating GLP-1 secretion. Studies in enteroendocrine cell models have shown that dietary peptides, amino acids, and phytochemicals, such as quercetin, can directly stimulate GLP-1 secretion. In our animal experiments, these food factors improved glucose metabolism and increased GLP-1 secretion. Furthermore, some dietary peptides not only stimulated GLP-1 secretion but also reduced plasma peptidase activity, which is responsible for GLP-1 inactivation. Herein, we review the relationship between GLP-1 and food factors, especially dietary peptides and flavonoids. Accordingly, utilization of food factors with GLP-1-releasing/enhancing activity is a promising strategy for preventing and treating obesity and diabetes.
  • Combination of α-Glycosyl-Isoquercitrin and Soybean Fiber Promotes Quercetin Bioavailability and Glucagon-like Peptide-1 Secretion and Improves Glucose Homeostasis in Rats Fed a High-Fat High-Sucrose Diet.
    Aphichat Trakooncharoenvit; Hiroshi Hara; Tohru Hira
    Journal of agricultural and food chemistry, 69, 21, 5907, 5916, 02 Jun. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, This study examined the effects of a combination of soybean fiber and α-glycosyl-isoquercitrin (AGIQ) on improving quercetin bioavailability and glucose metabolism in rats fed an obesogenic diet. For 9 weeks, rats were individually fed a control diet, a high-fat high-sucrose (H) diet, H with soybean fiber (HS), or with AGIQ (HQ), or with both (HSQ). Quercetin derivatives in plasma, feces, urine, and cecal content were quantified by high-performance liquid chromatography to assess the bioavailability of quercetin, and meal tolerance tests were performed to assess postprandial glycemia and glucagon-like peptide-1 (GLP-1) responses. The HSQ group had higher plasma quercetin levels than HQ. The postprandial glycemia was attenuated in the HSQ group when compared to the H group. The basal plasma GLP-1 concentrations positively correlated with plasma quercetin derivative concentrations. Hence, the combination of soybean fiber and AGIQ could be beneficial for reducing the risk of glucose intolerance, possibly involving enhanced quercetin bioavailability and GLP-1 secretion., 32209234;32209236
  • Acute Oral Calcium Suppresses Food Intake Through Enhanced Peptide-YY Secretion Mediated by the Calcium-Sensing Receptor in Rats.
    Akiho Igarashi; Shono Ogasawara; Ryo Takagi; Kazufumi Okada; Yoichi M Ito; Hiroshi Hara; Tohru Hira
    The Journal of nutrition, 151, 5, 1320, 1328, 11 May 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, BACKGROUND: Dietary calcium has been proposed to reduce appetite in human studies. Postprandial satiety is mainly controlled by gut hormones. However, the effect of calcium on appetite and the role of gut hormones remain unclear. OBJECTIVES: We examined whether oral administration of calcium reduces food intake in rats and investigated the underlying mechanism. METHODS: Male Sprague Dawley rats (8-12 wk old) were used after an overnight fastifffng. In a series of 2 trials with 1-wk interval between challenges, food intake was measured 0.5-24 h after oral gavage of a vehicle (saline containing 1.5% carboxymethyl cellulose) as the control treatment, or the vehicle containing various calcium compounds [calcium chloride (CaCl2), calcium carbonate, calcium lactate, in a random order] at 150 mg calcium/kg dose. A conditional taste aversion test was conducted. In separate experiments, plasma calcium and gut hormone concentrations were measured 15 or 30 min after oral administration of the calcium compounds. In anesthetized rats, portal peptide-YY (PYY) concentrations were measured after intraluminal administration of a liquid meal with or without additional calcium. RESULTS: Oral CaCl2 reduced food intake acutely (30 min, ∼20%, P < 0.05) compared with control rats, without taste aversion. Plasma PYY concentration was higher (100%, P < 0.05) in CaCl2-preloaded rats than in control rats, 15 min after administration. In anesthetized rats, luminal meal + CaCl2 induced a 4-fold higher increase in plasma PYY than the control treatment did. Oral administration of a calcium-sensing receptor (CaSR) agonist suppressed food intake (∼30%, P < 0.05), but CaCl2 and CaSR agonist did not suppress food intake under treatment with a PYY receptor antagonist. Furthermore, the CaSR antagonist attenuated the effect of CaCl2 on food intake. CONCLUSIONS: CaCl2 suppresses food intake partly by increasing CaSR-mediated PYY secretion in rats. Our findings could at least partially explain the satiating effect of calcium., 32209235
  • Glucagon-like peptide-1 response to whey protein is less diminished by dipeptidyl peptidase-4 in comparison with responses to dextrin, a lipid and casein in rats.
    Yuki Shimizu; Hiroshi Hara; Tohru Hira
    The British journal of nutrition, 125, 4, 398, 407, 28 Feb. 2021, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
    English, Scientific journal, Although glucose is the best-known nutrient to stimulate glucagon-like peptide-1 (GLP-1) secretion, dietary peptides also potently stimulate GLP-1 secretion. Certain peptide fragments derived from dietary proteins possess dipeptidyl peptidase-4 (DPP-4) inhibitory activity in vitro. Hence, we hypothesised that dietary peptides protect GLP-1 from degradation through attenuating DPP-4 activity in vivo. Here, we compared GLP-1 responses with dietary proteins, a carbohydrate and a lipid (Intralipos) in rats having or not having plasma DPP-4 activity. Plasma GLP-1 concentrations clearly increased by oral administration of whey protein (2-4 g/kg), but not by that of dextrin (2-4 g/kg), in control rats (untreated Sprague-Dawley rats and F344/Jcl rats), having DPP-4 activity. In contrast, dextrin administration increased the plasma GLP-1 concentrations as the whey protein administration did, in rats having reduced or no DPP-4 activity (a DPP-4 inhibitor, sitagliptin-treated Sprague-Dawley rats or DPP-4-deficient F344/DuCrl/Crlj rats). DPP-4 inhibition by sitagliptin treatment also enhanced GLP-1 response to Intralipos, and casein, but the treatment did not further enhance GLP-1 response to whey protein. Intestinal GLP-1 content and gastric emptying rate were not associated with differences in GLP-1 responses to test nutrients. The luminal contents from rats administered whey protein decreased DPP-4 activity in vitro. These results suggest that GLP-1 released by dextrin, Intralipos and casein was immediately degraded by DPP-4, while GLP-1 released by whey protein was less degraded. Our study provides novel in vivo evidence supporting the hypothesis that dietary peptides not only stimulate GLP-1 secretion but also inhibit DPP-4 activity to potentiate GLP-1 response., 32209235;32209234;11819850
  • Blood Sampling From Rat Ileal Mesenteric Vein Revealed a Major Role of Dietary Protein in Meal-Induced GLP-1 Response.
    Tohru Hira; Madoka Sekishita; Hiroshi Hara
    Frontiers in endocrinology, 12, 689685, 689685, 2021, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
    English, Scientific journal, The present study was conducted to examine region-dependent glucagon-like peptide-1 (GLP-1) responses to "meal ingestion" under physiological (conscious and unrestrained) conditions using rats with a catheter inserted into either the portal vein (PV) or the ileal mesenteric vein (ILMV). After recovery from the cannulation surgery, blood samples were collected from either PV or ILMV catheter before and after the voluntary ingestion of test diets. After an AIN-93G standard diet ingestion, GLP-1 concentration was higher in ILMV than in PV, and postprandial responses of peptide-YY (PYY) had similar trend, while that of glucose dependent-insulinotropic polypeptide showed an opposite trend to GLP-1/PYY responses. In a separated experiment, a protein-enriched diet containing casein at 25% wt/wt transiently increased GLP-1 concentration only in ILMV; however, a protein-free diet did not increase GLP-1 concentrations in PV or ILMV. These results indicate that postprandial GLP-1 is immediately released from the distal intestine under physiological conditions, and that dietary protein has a critical role in the enhancement of postprandial GLP-1 response., 32209239;32209235
  • Expression of serotonin receptor HTR4 in glucagon-like peptide-1-positive enteroendocrine cells of the murine intestine.
    Motoshi Okumura; Akihiro Hamada; Fumina Ohsaka; Takeshi Tsuruta; Tohru Hira; Kei Sonoyama
    Pflugers Archiv : European journal of physiology, 472, 10, 1521, 1532, Oct. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Impacts of Low-Digestible Carbohydrates and a Rare Sugar on Enteroendocrine Systems
    比良 徹; 原 博
    ルミナコイド研究 : 日本食物繊維学会会誌, 24, 1, 11, 18, 日本食物繊維学会, Jun. 2020, [Peer-reviewed], [Invited], [Lead author, Corresponding author], [Domestic magazines]
    Japanese
  • Water-soluble dietary fibers enhance bioavailability of quercetin and a fiber derived from soybean is most effective after long-term feeding in rats.
    Aphichat Trakooncharoenvit; Seiya Tanaka; Erika Mizuta; Tohru Hira; Hiroshi Hara
    European journal of nutrition, 59, 4, 1389, 1398, Jun. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • What Is GLP-1 Really Doing in Obesity?
    Tohru Hira; Jukkrapong Pinyo; Hiroshi Hara
    Trends in endocrinology and metabolism: TEM, 31, 2, 71, 80, Feb. 2020, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
    English, Scientific journal, 32209234;11819850;10695713
  • Correlation between 12α-hydroxylated bile acids and insulin secretion during glucose tolerance tests in rats fed a high-fat and high-sucrose diet.
    Reika Yoshitsugu; Keidai Kikuchi; Shota Hori; Hitoshi Iwaya; Masahito Hagio; Hidehisa Shimizu; Tohru Hira; Satoshi Ishizuka
    Lipids in health and disease, 19, 1, 9, 9, 15 Jan. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Oral preload of calcium reduces food intake via enhanced PYY secretion in rats
    Tohru Hira; Shono Ogasawara; Hiroshi Hara
    PROCEEDINGS OF THE NUTRITION SOCIETY, 79, OCE2, E239, E239, 2020
    English, International conference proceedings
  • Reply to the Letter: Increased bioavailability of plasma polyphenols via the intestinal fermentation of soybean fibers: a role for gut microbiome?
    Aphichat Trakooncharoenvit; Seiya Tanaka; Erika Mizuta; Tohru Hira; Hiroshi Hara
    European journal of nutrition, 58, 6, 2563, 2563, Sep. 2019, [Peer-reviewed], [International Magazine]
    English
  • Enhanced postprandial glucagon-like peptide-1 secretion during obesity development has a protective role against glucose intolerance induction in rats.
    Jukkrapong Pinyo; Tohru Hira; Hiroshi Hara
    The British journal of nutrition, 122, 4, 411, 422, 28 Aug. 2019, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, 11819850
  • Continuous feeding of a combined high-fat and high-sucrose diet, rather than an individual high-fat or high-sucrose diet, rapidly enhances the glucagon-like peptide-1 secretory response to meal ingestion in diet-induced obese rats.
    Jukkrapong Pinyo; Tohru Hira; Hiroshi Hara
    Nutrition (Burbank, Los Angeles County, Calif.), 62, 122, 130, Jun. 2019, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, 32209238
  • Casein materials show different digestion patterns using an in vitro gastrointestinal model and different release of glucagon-like peptide-1 by enteroendocrine GLUTag cells.
    Yosuke Komatsu; Yasuaki Wada; Hirohisa Izumi; Takashi Shimizu; Yasuhiro Takeda; Tohru Hira; Hiroshi Hara
    Food chemistry, 277, 423, 431, 30 Mar. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal
  • Wheat gluten hydrolysate potently stimulates peptide-YY secretion and suppresses food intake in rats.
    Wenya Chen; Tohru Hira; Shingo Nakajima; Hiroshi Hara
    Bioscience, biotechnology, and biochemistry, 82, 11, 1992, 1999, Nov. 2018, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal
  • Novel Mechanism of Fatty Acid Sensing in Enteroendocrine Cells: Specific Structures in Oxo-Fatty Acids Produced by Gut Bacteria Are Responsible for CCK Secretion in STC-1 Cells via GPR40.
    Tohru Hira; Shono Ogasawara; Asuka Yahagi; Minami Kamachi; Jiaxin Li; Saki Nishimura; Masayoshi Sakaino; Takatoshi Yamashita; Shigenobu Kishino; Jun Ogawa; Hiroshi Hara
    Molecular nutrition & food research, 62, 19, e1800146, Oct. 2018, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
    English, Scientific journal
  • Resistant maltodextrin or fructooligosaccharides promotes GLP-1 production in male rats fed a high-fat and high-sucrose diet, and partially reduces energy intake and adiposity
    Tohru Hira; Ryoya Suto; Yuka Kishimoto; Sumiko Kanahori; Hiroshi Hara
    EUROPEAN JOURNAL OF NUTRITION, 57, 3, 965, 979, Apr. 2018, [Peer-reviewed], [Lead author, Corresponding author]
    English, Scientific journal, 32209239
  • Secretion of GLP-1 but not GIP is potently stimulated by luminal d-Allulose (d-Psicose) in rats.
    Masaki Hayakawa; Tohru Hira; Masako Nakamura; Tetsuo Iida; Yuka Kishimoto; Hiroshi Hara
    Biochemical and biophysical research communications, 496, 3, 898, 903, 02 Feb. 2018, [Peer-reviewed], [Corresponding author], [International Magazine]
    English, Scientific journal, 32209237
  • GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose.
    Yusaku Iwasaki; Mio Sendo; Katsuya Dezaki; Tohru Hira; Takehiro Sato; Masanori Nakata; Chayon Goswami; Ryohei Aoki; Takeshi Arai; Parmila Kumari; Masaki Hayakawa; Chiaki Masuda; Takashi Okada; Hiroshi Hara; Daniel J Drucker; Yuichiro Yamada; Masaaki Tokuda; Toshihiko Yada
    Nature communications, 9, 1, 113, 113, 09 Jan. 2018, [Peer-reviewed], [Internationally co-authored], [International Magazine]
    English, Scientific journal
  • 消化管ホルモンup to date 食品ペプチドを利用した消化管内分泌系への作用
    比良徹; 中島進吾; 原博
    月刊消化器・肝臓内科, 3, 2, 140, 146, (有)科学評論社, 2018, [Invited], [Lead author]
    Japanese
  • Impact of difructose anhydride III, raffinose, and fructooligosaccharides on energy intake, gut hormones, and cecal fermentation in rats fed a high-fat and high-sucrose diet.
    Tohru Hira; Kurumi Yanagihara; Toshiki Koga; Keisuke Takahashi; Taizo Nagura; Hirokatsu Uchino; Hiroshi Hara
    Bioscience, biotechnology, and biochemistry, 81, 11, 2186, 2194, Nov. 2017, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
    English, Scientific journal, 32209238
  • Canagliflozin potentiates GLP-1 secretion and lowers the peak of GIP secretion in rats fed a high-fat high-sucrose diet.
    Tohru Hira; Toshiki Koga; Kazuyo Sasaki; Hiroshi Hara
    Biochemical and biophysical research communications, 492, 2, 161, 165, 14 Oct. 2017, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
    English, Scientific journal
  • 食品ペプチドで血糖を制御する
    Tohru HIRA
    KAGAKU TO SEIBUTSU, 55, 5, 296, 298, Japan Society for Bioscience, Biotechnology, and Agrochemistry, May 2017, [Peer-reviewed], [Lead author, Last author, Corresponding author]
    Scientific journal
  • Zinc directly stimulates cholecystokinin secretion from enteroendocrine cells and reduces gastric emptying in rats
    Shingo Nakajima; Tohru Hira; Hitoshi Iwaya; Hiroshi Hara
    MOLECULAR AND CELLULAR ENDOCRINOLOGY, 430, C, 108, 114, Jul. 2016, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • The calcium-sensing receptor in intestinal cells
    Tohru Hira; Shingo Nakajima; Hiroshi Hara
    Food and Nutritional Components in Focus, 2016-, 10, 396, 412, Royal Society of Chemistry, 2016, [Invited], [Lead author, Corresponding author]
    English, In book
  • Diunsaturated Aldehyde, trans,trans-2,4-Decadienal in the Intestinal Lumen Suppresses Gastric Emptying through Serotonin Signaling in Rats
    Tohru Hira; Asuka Yahagi; Said Nishimura; Masayoshi Sakaino; Takatoshi Yamashita; Hiroshi Hara
    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 63, 37, 8177, 8181, Sep. 2015, [Peer-reviewed], [Lead author, Corresponding author]
    English, Scientific journal
  • Resistant maltodextrin promotes fasting glucagon-like peptide-1 secretion and production together with glucose tolerance in rats
    Tohru Hira; Asuka Ikee; Yuka Kishimoto; Sumiko Kanahori; Hiroshi Hara
    BRITISH JOURNAL OF NUTRITION, 114, 1, 34, 42, Jul. 2015, [Peer-reviewed], [Lead author, Corresponding author]
    English, Scientific journal
  • Postprandial glucagon-like peptide-1 secretion is increased during the progression of glucose intolerance and obesity in high-fat/high-sucrose diet-fed rats
    Shingo Nakajima; Tohru Hira; Hiroshi Hara
    BRITISH JOURNAL OF NUTRITION, 113, 9, 1477, 1488, May 2015, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Rice protein hydrolysates stimulate GLP-1 secretion, reduce GLP-1 degradation, and lower the glycemic response in rats
    Yuki Ishikawa; Tohru Hira; Daisuke Inoue; Yukikazu Harada; Hiroyuki Hashimoto; Mikio Fujii; Motoni Kadowaki; Hiroshi Hara
    FOOD & FUNCTION, 6, 8, 2525, 2534, 2015, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Dietary sweet potato (Ipomoea batatas L.) leaf extract attenuates hyperglycaemia by enhancing the secretion of glucagon-like peptide-1 (GLP-1)
    Rika Nagamine; Shiori Ueno; Masahito Tsubata; Kazuya Yamaguchi; Kinya Takagaki; Tohru Hira; Hiroshi Hara; Takanori Tsuda
    FOOD & FUNCTION, 5, 9, 2309, 2316, Sep. 2014, [Peer-reviewed]
    English, Scientific journal
  • A nondigestible saccharide, fructooligosaccharide, increases the promotive effect of a flavonoid, alpha-glucosyl-isoquercitrin, on glucagon-like peptide 1 (GLP-1) secretion in rat intestine and enteroendocrine cells
    Panchita Phuwamongkolwiwat; Tohru Hira; Hiroshi Hara
    MOLECULAR NUTRITION & FOOD RESEARCH, 58, 7, 1581, 1584, Jul. 2014, [Peer-reviewed]
    English, Scientific journal
  • Activation of the gut calcium-sensing receptor by peptide agonists reduces rapid elevation of plasma glucose in response to oral glucose load in rats
    Maya Muramatsu; Tohru Hira; Arimi Mitsunaga; Eri Sato; Shingo Nakajima; Yoshiro Kitahara; Yuzuru Eto; Hiroshi Hara
    AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 306, 12, C1099, C1107, Jun. 2014, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Unsaturated aldehydes induce CCK secretion via TRPA1 in STC-1 cells
    Shingo Nakajima; Tohru Hira; Asuka Yahagi; Chigusa Nishiyama; Takatoshi Yamashita; Jun Imagi; Hiroshi Hara
    MOLECULAR NUTRITION & FOOD RESEARCH, 58, 5, 1042, 1051, May 2014, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Fructooligosaccharide augments benefits of quercetin-3-O-beta-glucoside on insulin sensitivity and plasma total cholesterol with promotion of flavonoid absorption in sucrose-fed rats
    Panchita Phuwamongkolwiwat; Takuya Suzuki; Tohru Hira; Hiroshi Hara
    EUROPEAN JOURNAL OF NUTRITION, 53, 2, 457, 468, Mar. 2014, [Peer-reviewed]
    English, Scientific journal
  • 松田 朋子、神谷 智康、草場 宣延、高野 晃、池口 主弥、高垣 欣也、石橋 千和、比良 徹、原 博
    Effectiveness of Potato Extract in Suppressing Food Intake and Stimulating Satiety
    薬理と治療, 42, 3, 211, 216, Mar. 2014, [Peer-reviewed]
  • Oral Administration of Corn Zein Hydrolysate Stimulates GLP-1 and GIP Secretion and Improves Glucose Tolerance in Male Normal Rats and Goto-Kakizaki Rats
    Noriyuki Higuchi; Tohru Hira; Nao Yamada; Hiroshi Hara
    ENDOCRINOLOGY, 154, 9, 3089, 3098, Sep. 2013, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Activation of gut calcium-sensing receptor by peptide agonists promotes glucose tolerance in rats
    Tohru Hira; Maya Muramatsu; Arimi Mitsunaga; Eri Sato; Shingo Nakajima; Yoshiro Kitahara; Yuzuru Eto; Hiroshi Hara
    FASEB JOURNAL, 27, Apr. 2013
    English, International conference proceedings
  • Glycochenodeoxycholic acid promotes proliferation of intestinal epithelia via reduction of cyclic AMP and increase in H2AX phosphorylation after exposure to gamma-rays
    Satoshi Ishizuka; Maiko Shiwaku; Masahito Hagio; Takuya Suzuki; Tohru Hira; Hiroshi Hara
    BIOMEDICAL RESEARCH-TOKYO, 33, 3, 159, 165, Jun. 2012, [Peer-reviewed]
    English, Scientific journal
  • Suppressive Effect on Food Intake of a Potato Extract (Potein (R)) Involving Cholecystokinin Release in Rats
    Wenya Chen; Tohru Hira; Shingo Nakajima; Hiroshi Tomozawa; Masahito Tsubata; Kazuya Yamaguchi; Hiroshi Hara
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 76, 6, 1104, 1109, Jun. 2012, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Calcium-sensing receptor mediates dietary peptide-induced CCK secretion in enteroendocrine STC-1 cells
    Shingo Nakajima; Tohru Hira; Hiroshi Hara
    MOLECULAR NUTRITION & FOOD RESEARCH, 56, 5, 753, 760, May 2012, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Acute effect of soybean beta-conglycinin hydrolysate ingestion on appetite sensations in healthy humans
    Tohru Hira; Naomi Mori; Toshihiro Nakamori; Hitoshi Furuta; Kozo Asano; Hitoshi Chiba; Hiroshi Hara
    APPETITE, 57, 3, 765, 768, Dec. 2011, [Peer-reviewed], [Lead author, Corresponding author]
    English, Scientific journal
  • The G-protein on cholesterol-rich membrane microdomains mediates mucosal sensing of short-chain fatty acid and secretory response in rat colon
    T. Yajima; R. Inoue; M. Yajima; T. Tsuruta; S. Karaki; T. Hira; A. Kuwahara
    ACTA PHYSIOLOGICA, 203, 3, 381, 389, Nov. 2011, [Peer-reviewed]
    English, Scientific journal
  • Potato Extract (Potein) Suppresses Food Intake in Rats through Inhibition of Luminal Trypsin Activity and Direct Stimulation of Cholecystokinin Secretion from Enteroendocrine Cells
    Shingo Nakajima; Tohru Hira; Masahito Tsubata; Kinya Takagaki; Hiroshi Hara
    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 59, 17, 9491, 9496, Sep. 2011, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Soybean beta-Conglycinin Bromelain Hydrolysate Stimulates Cholecystokinin Secretion by Enteroendocrine STC-1 Cells to Suppress the Appetite of Rats under Meal-Feeding Conditions
    Md. Kaosar Niaz Bin Sufian; Tohru Hira; Toshihiro Nakamori; Hitoshi Furuta; Kozo Asano; Hiroshi Hara
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 75, 5, 848, 853, May 2011, [Peer-reviewed]
    English, Scientific journal
  • GLP-1 Secretion in Response to Oral and Luminal Palatinose (Isomaltulose) in Rats
    Tohru Hira; Maya Muramatsu; Masahiro Okuno; Hiroshi Hara
    JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY, 57, 1, 30, 35, Feb. 2011, [Peer-reviewed], [Lead author, Corresponding author]
    English, Scientific journal
  • インクレチン分泌を刺激する食品ペプチド,アミノ酸 消化管内分泌細胞による栄養素認識,Nutrient‐sensingの解明と応用に期待
    比良 徹
    化学と生物, 49, 1, 11, 13, Japan Society for Bioscience, Biotechnology, and Agrochemistry, 2011, [Peer-reviewed], [Lead author, Last author, Corresponding author]
    Scientific journal
  • The Corn Protein, Zein Hydrolysate, Administered into the Ileum Attenuates Hyperglycemia via Its Dual Action on Glucagon-Like Peptide-1 Secretion and Dipeptidyl Peptidase-IV Activity in Rats
    Taisuke Mochida; Tohru Hira; Hiroshi Hara
    ENDOCRINOLOGY, 151, 7, 3095, 3104, Jul. 2010, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • Soybean beta 51-63 peptide stimulates cholecystokinin secretion via a calcium-sensing receptor in enteroendocrine STC-1 cells
    Shingo Nakajima; Tohru Hira; Yuzuru Eto; Kozo Asano; Hiroshi Hara
    REGULATORY PEPTIDES, 159, 1-3, 148, 155, Jan. 2010, [Peer-reviewed], [Corresponding author]
    English, Scientific journal
  • GLP-1 secretion is enhanced directly in the ileum but indirectly in the duodenum by a newly identified potent stimulator, zein hydrolysate, in rats
    Tohru Hira; Taisuke Mochida; Kyoko Miyashita; Hiroshi Hara
    AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 297, 4, G663, G671, Oct. 2009, [Peer-reviewed], [Lead author, Corresponding author]
    English, Scientific journal
  • Administration of anti-glucagon-like peptide-2 serum suppresses epithelial cell proliferation of the distal small intestine in weanling rats
    Satoshi Ishizuka; Ayako Inafune; Tohru Hira; Hirohisa Izumi; Kazuhiro Ozawa; Mitsunori Takase; Hiroshi Hara
    BIOMEDICAL RESEARCH-TOKYO, 30, 4, 259, 261, Aug. 2009, [Peer-reviewed]
    English, Scientific journal
  • alpha-Lactalbumin Hydrolysate Stimulates Glucagon-Like Peptide-2 Secretion and Small Intestinal Growth in Suckling Rats
    Hirohisa Izumi; Satoshi Ishizuka; Ayako Inafune; Tohru Hira; Kazuhiro Ozawa; Takashi Shimizu; Mitsunori Takase; Hiroshi Hara
    JOURNAL OF NUTRITION, 139, 7, 1322, 1327, Jul. 2009, [Peer-reviewed]
    English, Scientific journal
  • Cholecystokinin secretion induced by beta-conglycinin peptone depends on G alpha q-mediated pathways in enteroendocrine cells
    Tohru Hira; Toshihiro Maekawa; Kozo Asano; Hiroshi Hara
    EUROPEAN JOURNAL OF NUTRITION, 48, 2, 124, 127, Mar. 2009, [Peer-reviewed], [Lead author, Corresponding author]
    English, Scientific journal
  • Calcium-sensing receptor mediates phenylalanine-induced cholecystokinin secretion in enteroendocrine STC-1 cells
    Tohru Hira; Shingo Nakajima; Yuzuru Eto; Hiroshi Hara
    FEBS JOURNAL, 275, 18, 4620, 4626, Sep. 2008, [Peer-reviewed], [Lead author, Corresponding author]
    English, Scientific journal
  • Peptides derived from dolicholin, a phaseolin-like protein in country beans (Dolichos lablab), potently stimulate cholecystokinin secretion from Enteroendocrine STC-1 cells
    Md. Kaosar Nlaz Bin Suman; Tohru Hira; Kozo Asano; Hiroshi Hara
    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 55, 22, 8980, 8986, Oct. 2007, [Peer-reviewed]
    English, Scientific journal
  • Sucrose fatty acid esters suppress pancreatic secretion accompanied by peptide YY release in pancreatico-biliary diverted rats
    Tohru Hira; Katsuhiko Takahashi; Hiroshi Hara
    EXPERIMENTAL PHYSIOLOGY, 92, 4, 687, 694, Jul. 2007, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Pork peptone stimulates cholecystokinin secretion from enteroendocrine cells and suppresses appetite in rats
    M. K. N. B. Sufian; Tohru Hira; Kyoko Miyashita; Takashi Nishi; Kozo Asano; Hiroshi Hara
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 70, 8, 1869, 1874, Aug. 2006, [Peer-reviewed]
    English, Scientific journal
  • Mouse GPR40 heterologously expressed in Xenopus oocytes is activated by short-, medium-, and long-chain fatty acids
    G Stewart; T Hira; A Higgins; CP Smith; JT McLaughlin
    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 290, 3, C785, C792, Mar. 2006, [Peer-reviewed]
    English, Scientific journal
  • Multiple fatty acid sensing mechanisms operate in enteroendocrine cells - Novel evidence for direct mobilization of stored calcium by cytosolic fatty acid
    T Hira; AC Elliott; DG Thompson; RM Case; JT McLaughlin
    JOURNAL OF BIOLOGICAL CHEMISTRY, 279, 25, 26082, 26089, Jun. 2004, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Casein binds to the cell membrane and induces intracellular calcium signals in the enteroendocrine cell: A brief communication
    T Hira; H Hara; F Tomita; Y Aoyama
    EXPERIMENTAL BIOLOGY AND MEDICINE, 228, 7, 850, 854, Jul. 2003, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • L-homoarginine suppresses exocrine pancreas in rats
    T Hira; S Ohyama; H Hara
    AMINO ACIDS, 24, 4, 389, 396, 2003, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Dietary protein peptic hydrolysates stimulate cholecystokinin release via direct sensing by rat intestinal mucosal cells
    T Nishi; H Hara; T Hira; F Tomita
    EXPERIMENTAL BIOLOGY AND MEDICINE, 226, 11, 1031, 1036, Dec. 2001, [Peer-reviewed]
    English, Scientific journal
  • Dietary protein peptic hydrolysates stimulate cholecystokinin release via direct sensing by rat intestinal mucosal cells
    Takashi Nishi; Hirosh Hara; Tohru Hira; Fusao Tomita
    Experimental Biology and Medicine, 226, 11, 1031, 1036, Dec. 2001, [Peer-reviewed]
    English, Scientific journal
  • Endogenous cholecystokinin plays a role in down-regulation of pancreatic amylase independent of dietary carbohydrate in rats
    H Hara; S Ohyama; T Hira
    REGULATORY PEPTIDES, 99, 2-3, 103, 110, Jun. 2001, [Peer-reviewed], [Last author]
    English, Scientific journal
  • Characterization of binding between the rat small intestinal brush-border membrane and dietary proteins in the sensory mechanism of luminal dietary proteins
    T Hira; H Hara; F Tomita
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 65, 5, 1007, 1015, May 2001, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Luminal dietary protein, not amino acids, induces pancreatic protease via CCK in pancreaticobiliary-diverted rats
    H Hara; S Ohyama; T Hira
    AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 278, 6, G937, G945, Jun. 2000, [Peer-reviewed], [Last author]
    English, Scientific journal
  • Stimulative effect of a casein hydrolysate on exocrine pancreatic secretion that is independent of luminal trypsin inhibitory activity in rats
    T Hira; H Hara; Y Aoyama
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 63, 7, 1192, 1196, Jul. 1999, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Effects of DFA IV in rats: Calcium absorption and metabolism of DFA IV by intestinal microorganisms
    K Saito; T Hira; T Suzuki; H Hara; A Yokota; F Tomita
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 63, 4, 655, 661, Apr. 1999, [Peer-reviewed]
    English, Scientific journal
  • Guanidino group is involved in the stimulation of exocrine pancreatic secretion by protamine in normal and chronic bile pancreatic juice-diverted rats
    T Hira; H Hara; T Kasai
    PANCREAS, 18, 2, 165, 171, Mar. 1999, [Peer-reviewed], [Lead author]
    English, Scientific journal
■ Other Activities and Achievements
■ Books and other publications
  • ペプチドの生体調節機能と応用
    比良 徹; 分担執筆; 松井利郎; 監修, 第14章 消化管ホルモン調節ペプチド
    シーエムシー出版, Jul. 2024, 9784781318097, viii, 253p, Japanese
  • 食品免疫学事典
    比良 徹, 9章(9-13) 消化管内分泌系を介した作用
    朝倉書店, Nov. 2021, [Contributor]
  • 食品免疫学事典
    比良 徹; 原 博, 2章(2-14) 消化管ホルモン
    朝倉書店, Nov. 2021, [Contributor]
  • エッセンシャル栄養化学 (KS農学専門書)
    比良 徹, 第3章 体内での栄養素の動態:消化・吸収・分布・代謝・排泄
    講談社, 27 Aug. 2021, 4065238064, 320, Japanese, [Contributor]
  • 腸内細菌-宿主のクロストークとこれを修飾する食事要因
    比良 徹; 原 博, 難消化性糖質の消化管内分泌系への作用
    建帛社, May 2019, [Contributor]
  • 機能性食品開発のための初期評価試験プロトコール集
    比良 徹; 原 博, ラットを用いた食欲抑制試験、GLUTag 細胞を用いた GLP-1 分泌試験、STC-1 細胞を用いた CCK 分泌試験
    シーエムシー出版, Oct. 2017, [Contributor]
  • The Calcium-sensing Receptor in Intestinal Cells / Calcium : Chemistry, Analysis, Function and Effects / Food and Nutritional Components in Focus
    Hira T.; Nakajima S.; Hara H., 396-412
    The Royal Society of Chemistry, Oct. 2015, [Contributor]
  • 機能性タンパク質・ペプチドと生体利用
    原 博; 比良 徹, 消化管内分泌系を介して作用する機能性ペプチド
    建帛社, May 2010, [Contributor]
  • 腸管細胞機能実験法
    原 博; 西 隆司; 比良 徹, 上皮細胞機能の実験法 コレシストキンン産生細胞株STC-1における細胞内カルシウム濃度変化の測定
    学会出版センター, Oct. 2005, 274, 88-96, [Contributor]
■ Lectures, oral presentations, etc.
  • 化学受容、機械受容を介した消化管ホルモンGLP-1分泌促進機構
    比良 徹
    2026年度 日本農芸化学会東北・北海道支部 合同支部会, 03 Oct. 2026
    [Invited]
  • 農産物等由来食品が満腹感を与えるメカニズム ―食事成分による肥満・糖尿病の予防へ―
    比良 徹
    北海道大学創基150周年記念シンポジウム in 東京, 22 Aug. 2026
    [Invited]
  • 食品成分の化学受容、機械受容を介した GLP-1 分泌促進機構
    比良 徹
    第80回日本栄養・食糧学会大会 シンポジウム, 17 May 2026, Nominated symposium
  • 食事誘導性肥満における栄養素応答性GLP-1分泌の適応
    比良 徹
    第55回日本栄養・食糧学会北海道支部シンポジウム, 22 Sep. 2025
    [Invited]
  • 食品タンパク質によるGLP-1分泌促進と体温上昇作用
    比良 徹
    インクレチン研究会2025, 05 Apr. 2025, Oral presentation
    [Invited]
  • 動物実験の新しい展開 食事誘導性肥満モデル、血管カニュレーションモデルを用いた、消化管ホルモンGLP-1の分泌調節に関する研究
    比良 徹
    第78回日本栄養・食糧学会大会, 25 May 2024
    [Invited]
  • GLP-1産生消化管内分泌細胞が認識するペプチド構造
    比良 徹
    日本農芸化学会2023年度大会, 27 Mar. 2024
    [Invited]
  • 希少糖D-アルロースによるGLP-1分泌促進機構
    比良 徹
    第14回日本安定同位体・生体ガス医学応用学会大会, 09 Dec. 2023, Nominated symposium
    [Invited]
  • 食品成分による消化管ホルモン分泌の調節
    比良 徹
    第111回日本栄養・食糧学会関東支部シンポジウム, 14 Oct. 2023, Nominated symposium
    [Invited]
  • 食品タンパク質・ペプチドによる GLP-1 分泌促進とそれによる血糖上昇抑制、 体温上昇作用
    比良 徹
    第77回日本栄養・食糧学会大会, 13 May 2023, Nominated symposium
  • 食品成分による消化管ホルモンの分泌
    比良 徹
    第3回 ファーマラボ EXPO 大阪, 09 Mar. 2023, Public discourse
  • 食におけるタンパク質の重要性について
    比良 徹
    令和4年度地域バイオ育成講座講演会, 30 Jan. 2023, Public discourse
    [Invited]
  • Adaptive changes in nutrient-induced GLP-1 secretion in diet-induced obese model rats
    Tohru Hira
    22nd IUNS-ICN International Congress of Nutritio, 08 Dec. 2022, Nominated symposium
  • 食品ペプチドによるGLP-1分泌促進と分解抑制
    比良 徹
    日本アミノ酸学会第9回夏のシンポジウム, 27 Aug. 2022, Nominated symposium
    [Invited]
  • 消化管内分泌系への作用を介する糖代謝改善ペプチド
    比良 徹
    日本農芸化学会2021年度大会, 20 Mar. 2021, Nominated symposium
    [Invited]
  • trans,trans-2,4-Decadienal stimulates cholecystokinin secretion in enteroendocrine cells, and suppresses gastric emptying in rats
    Tohru Hira
    International symposium on lipids and food ingredients for health promotion, 12 Mar. 2021, Oral presentation
    [Invited]
  • 難消化性糖質の消化管内分泌系への作用
    比良 徹
    日本食物繊維学会第24回学術集会, 02 Nov. 2019, Japanese, Nominated symposium
    [Invited], [Domestic Conference]
  • " 食品成分による消化管内分泌系のコントロール 主にGLP-1に関して"
    比良 徹
    第98回北海道医学大会生理系分科会・日本生理学会北海道地方会, 06 Oct. 2018, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • 難消化性糖質の消化管内分泌系への作用
    比良 徹; 原 博
    第72回日本栄養・食糧学会大会 共催:Hindgut Club Japan, 12 May 2018, Public symposium
    [Invited]
  • GLP-1を増やす食品成分、食事条件
    比良 徹
    平成29年度 公益社団法人日本農芸化学会 北海道支部第2回講演会および公益社団法人日本栄養・食糧学会 第47回北海道支部大会合同大会, 02 Dec. 2017, Japanese, Nominated symposium
    [Domestic Conference]
  • 消化管に働きかけて血糖上昇を抑制する食品ペプチド
    比良 徹
    第3回食科学プラットフォームセミナー, 14 Jul. 2017, Public discourse
    [Invited]
  • 食品成分による消化管ホルモン分泌調節
    比良 徹
    第18回日本神経消化器病学会、第6回IBS研究会、第84回消化器心身医学研究会、第10回機能性ディスペプシア研究会 合同学術集会2016, 10 Sep. 2016, Nominated symposium
    [Invited]
  • 米ペプチドによる消化管ホルモン分泌を介した血糖上昇抑制作用
    比良徹, 原博
    第70回日本栄養・食糧学会大会, 15 May 2016, Japanese, Nominated symposium
    [Invited]
  • 難消化性デキストリンのチカラ-消化管ホルモンを介した新たな機能-
    HIRA Tohru
    第70回日本栄養・食糧学会大会 ランチョンセミナー, 14 May 2016, Public discourse
    [Invited]
  • trans,trans-2,4-デカジエナールの胃排出抑制機構
    比良 徹
    Hindgut Club Japanサテライトシンポジウム, 14 May 2016, Nominated symposium
    [Invited]
  • 血糖調節ペプチド
    比良 徹
    日本農芸化学会2015年度大会, 28 Mar. 2016, Nominated symposium
    [Invited]
  • 食品成分による消化管ホルモン分泌の制御と作用機構
    比良 徹
    第93回日本生理学会大会, 23 Mar. 2016, Nominated symposium
    [Invited]
  • 食事誘導性肥満の発症過程におけるGLP-1分泌応答〜ラットでの食事負荷試験による解析
    比良 徹
    第21回Hindgut club Japanシンポジウム, 05 Dec. 2015, Nominated symposium
    [Invited]
  • 食事誘導性肥満モデルラットにおける食後GLP-1分泌応答
    比良 徹
    第27回夏期油脂・コレステロール研究会, 18 Jul. 2015, Nominated symposium
    [Invited]
  • 食品ペプチドによる消化管内分泌系への作用を介した血糖調節
    比良 徹
    北大リサーチ&ビジネスパークセミナー おいしくてヘルシーな北海道! ~新たなフードサイエンスとビジネス環境へ~, 26 Nov. 2014, Public discourse
    [Invited]
  • Effects of resistant maltodextrin and fructooligosaccharides on fasting GLP-1 levels and glucose tolerance in rats
    Tohru Hira
    10th Vahouny Dietary Fiber Symposium, 28 Mar. 2014, Nominated symposium
  • 食品ペプチドの消化管での作用を介した血糖制御に関する研究
    比良徹
    2013年度日本アミノ酸学会 科学・技術賞受賞講演, 02 Nov. 2013, Japanese
    [Invited]
  • 食品ペプチドによるGLP-1分泌を介した血糖上昇抑制
    比良 徹
    2013年度 生理学研究所研究会 上皮膜輸送の多層的コントロールによる生体の恒常性維持機構, 26 Aug. 2013, Nominated symposium
    [Invited]
  • 消化管内分泌系調節ペプチド
    原博, 比良徹
    第67回日本栄養・食糧学会大会S10-03「ペプチドが拓く健康科学の新しい世界」, 26 May 2013, Japanese
■ Syllabus
  • 大学院共通授業科目(一般科目):自然科学・応用科学, 2024年, 修士課程, 大学院共通科目
  • 食品科学特論, 2024年, 修士課程, 農学院
  • 食品科学特論演習, 2024年, 修士課程, 農学院
  • 一般教育演習(フレッシュマンセミナー), 2024年, 学士課程, 全学教育
  • 栄養化学Ⅱ, 2024年, 学士課程, 農学部
  • 生物機能化学実験Ⅳ, 2024年, 学士課程, 農学部
  • 生物学Ⅰ, 2024年, 学士課程, 全学教育
  • 化学概論, 2024年, 学士課程, 農学部
■ Affiliated academic society
  • 日本農芸化学会
  • 日本栄養・食糧学会
  • 日本アミノ酸学会
  • 日本糖尿病学会
  • 日本肥満学会
  • 日本食物繊維学会
■ Research Themes
  • 食事誘導性肥満におけるGLP-1分泌応答増大の理解と活用
    科学研究費助成事業
    Apr. 2026 - Mar. 2029
    比良 徹
    日本学術振興会, 基盤研究(B), 北海道大学, Principal investigator, 26K01693
  • GLP-1分泌促進と分解抑制の両作用を併せ持つペプチドの創生
    科学研究費助成事業
    Jun. 2024 - Mar. 2026
    比良 徹
    日本学術振興会, 挑戦的研究(萌芽), 北海道大学, Principal investigator, 24K21844
  • Protective mechanisms of enteroendocrine systems against diet-induced obesity and glucose intolerance
    Grants-in-Aid for Scientific Research
    01 Apr. 2022 - 31 Mar. 2025
    比良 徹
    2023年度は、GLP-1分泌を促進することが知られる脂肪酸であるα-リノレン酸を豊富に含有するえごま油を、【1】食事誘導性肥満モデルラット、および【1】糖尿病モデルラットに長期摂取させて、GLP-1分泌や耐糖能へ与える影響を検討した。
    【1】において、ラードを主とする高脂肪食に対し、一部および大部分をえごま油で置換した高脂肪食をラットに長期摂取させた。その結果、高脂肪食の油脂の大部分をえごま油に置換すると、栄養素応答性のGLP-1分泌が増大する傾向が見られた。食後血糖の改善は見られなかったが、空腹時血糖の改善傾向は観察された。さらに血中脂質濃度の低下作用が見られた。これらの結果から、高えごま油食の長期摂取はGLP-1分泌を増大すること、空腹時の糖代謝や脂質代謝を改善する可能性が示唆された。
    【2】において、糖尿病モデルラット(Goto-Kakizakiラット)において、普通食に含まれる大豆油をえごま油に置換して長期摂取させた。食事負荷試験において、GLP-1分泌応答への影響は見られなかったが、血糖上昇の抑制ならびにインスリン分泌の増大傾向が見られた。また、インスリン負荷試験においては、普通食摂取群に比べてえごま油摂取群の方がインスリン投与により血糖がより低下し、インスリン感受性が改善していることが示唆された。これらの結果より、えごま油摂取は、遺伝的糖尿病モデルにおいて、GLP-1分泌促進には依存せずに、耐糖能を改善することが示唆された。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 23K23544
  • 食事誘導性肥満・耐糖能異常を防ぐ消化管内分泌系の適応機構
    科学研究費助成事業 基盤研究(B)
    Apr. 2022 - Mar. 2025
    比良 徹
    日本学術振興会, 基盤研究(B), 北海道大学, 22H02277
  • Mechanisms underlying enhanced GLP-1 response in diet-induced obesity
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2019 - 31 Mar. 2022
    比良 徹
    消化管ホルモンGLP-1は、食事刺激により消化管内分泌細胞から分泌され、インスリン分泌増強や食欲抑制などをもたらす。これまでに、食事誘導性の肥満や耐糖能異常の発症過程で、食後GLP-1分泌が増大することを見出した。しかし、消化管および消化管内分泌細胞にどのような変化が生じているのかは不明であり、本研究課題は、これを詳細に解析し、その分子メカニズムを明らかにすることを目的とする。
    はじめに、遺伝的糖尿病モデルラット(Goto-Kakizakiラット)と正常ラットそれぞれに、普通食または高脂肪高ショ糖食を長期間(6ヶ月)摂取させ、2または4週おきに食事負荷試験を実施した。食事負荷試験の際は、全ての群において経腸栄養剤を一定量経口投与した。糖尿病モデルラットと正常ラットともに、高脂肪高ショ糖食の長期摂取により耐糖能不全が生じたが、その程度は糖尿病モデルラットの方が顕著であった。食後GLP-1分泌は、正常ラットでは高脂肪高ショ糖食の持続摂取により増大し、その増大は実験終了時(6ヶ月後)まで維持された。一方で糖尿病モデルラットではそのような増大は見られなかった。このことから、正常なラットでは長期間の肥満誘導食の持続摂取でも食後GLP-1分泌応答は増大すること、そのような適応は遺伝的糖尿病モデルでは生じないことが明らかとなった。食事誘導性肥満におけるGLP-1分泌の増大は、耐糖能の悪化に対して防御的な適応と考えられ、このような適応機構の欠如が糖尿病へと進展する要因の一つであると考えられた。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 19K05860
  • Study on postprandial nutrient and gut hormone responses in different intestinal regions
    Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)
    29 Jun. 2018 - 31 Mar. 2020
    Hara Hiroshi
    Changes in plasma nutrient (glucose) levels and gut hormone levels after meal, in different intestinal regions have not been well characterized.
    We established experimental rat model equipped with a catheter inserted into the ileal mesenteric vein, or the portal vein. After the oral administration of meal having different compositions, plasma glucose levels and gut hormone levels had different responses, dependent on the meal composition, and on the intestinal region of blood sampling.
    These results demonstrate that the rat model is available for investigating regional nutrient absorption and gut hormone secretion under a physiological condition.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), 18K19158
  • Study on physiological effects of isomalto-megalo-saccharides
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    01 Apr. 2017 - 31 Mar. 2020
    Hara Hiroshi
    Isomalto-megalo-saccharides are novel saccharides having unique structures. Various health promotive functions are expected due to their specific interactions with food components and with target cells in the gastrointestinal tract.
    In an intestinal epithelial cell model (Caco2), isomalto-megalo-saccharides prevented impairment of gut barrier function by lipid oxidation products.In animal studies using rats, isomalto-megalo-saccharides enhanced intestinal absorption of quercetin. Furthermore, the combination of isomalto-megalo-saccharides and quercetin potently stimulated secretion of a gastrointestinal hormone, GLP-1.
    These results demonstrate beneficial effects of isomalto-megalo-saccharides, as a functional food factor.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), 17H01473
  • Regulation of gut nutrient sensing mechanisms in response to dietary intervention
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2016 - 31 Mar. 2019
    Hira Tohru
    We have previously demonstrated that continuous feeding of a high fat and high sucrose diet enhanced nutrient-induced GLP-1 secretion in rats. In this research project, we revealed that the high fat diet, rather than the high sucrose diet, has potent impact on enhancement of nutrient-induced GLP-1 secretion. In addition, the adaptive changes in nutrient-induced GLP-1 secretion was rapidly occurred in young rats than adult rats. Furthermore, by conducting continuous administration of GLP-1 receptor antagonist, we found that the increased GLP-1 response has a role to prevent from glucose intolerance during the development of diet-induced obesity.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 16K07725
  • Study on sensing mechanism of low-digestible saccharides in nutrient-sensing enteroendocrine cells
    Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    01 Apr. 2016 - 31 Mar. 2018
    Hara Hiroshi
    We examined the effects of indigestible saccharides including rare sugar D-allulose on a gut hormone GLP-1 secretion. Single oral administration of resistant maltodextrin (RMD) or D-allulose potently stimulated GLP-1 secretion in rats. D-allulose had larger and continuous stimulatory effect on GLP-1 secretion than RMD. The GLP-1-stimulating effect was observed by oral and luminal but not by intraperitoneal administration of D-allulose, indicating D-allulose exerted the effect in the intestinal lumen. These results demonstrate important role of enteroendocrine cell to sense indigestible saccharides in gut hormone secretions under a physiological condition.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 16K14918
  • 食事条件に対する消化管栄養素感受性の適応機構の解明と制御
    基盤研究(C)
    Apr. 2016 - Mar. 2018
    比良 徹
    文部科学省, Principal investigator, Competitive research funding
  • Study on enteroendocrine, nervous and reproductive systems related to diet for preventing metabolic diseases.
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    01 Apr. 2014 - 31 Mar. 2017
    Hara Hiroshi
    In this project, we investigated gut hormone secretory responses to ‘meal’in the conscious animal model equipped with portal cannula. We have found that gut hormone responses (such as GLP-1, GIP,PYY, Ghrelin) are modified by changing the source of dietary proteins. Furthermore, the effect of dietary protein was modified by the source of carbohydrates in the meal.
    Feeding the diet supplemented with resistant maltodextrin which has GLP-1-releasing activity prevented excess energy intake induced by high fat high sucrose diet.
    Our results suggest that postprandial gut hormone responses can be desirably manipulated by changing the composition of a meal.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, 26252016
  • Role of GLP-1 during the development of diet-induced obesity and glucose impairment
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    01 Apr. 2013 - 31 Mar. 2016
    HIRA Tohru
    It is unclear how postprandial GLP-1 secretory response is affected during the development of diet-induced obesity. Meal tolerance test (MTT) was conducted in rats fed normal or high-fat/high-sucrose (HF/HS) diet, and postprandial GLP-1, insulin and glycemic response were monitored.
    Postprandial GLP-1 secretion was larger in HF/HS rats than control rats at week 2 and 4, and this was reflected by increased insulin response in HF/HS rats. In the intestinal mucosa, among various nutrient sensing receptors and transporters evaluated, one of fatty acid receptors, FFAR1 had higher mRNA expression in the upper small intestine of HF/HS rats compared to that of control rats.
    These result demonstrates that postprandial GLP-1 secretion is increased in the early period of developing diet-induced obesity, and that increased postprandial GLP-1 response contributes to normalize postprandial glycemic response by enhancing insulin secretion.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 25450159
  • Elucidation of mechanisms to avoid chronic inflammation via enteroendocrine system: relationships between immune cells and adipocytes
    Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    01 Apr. 2012 - 31 Mar. 2015
    ISHIZUKA Satoshi; HIRA Tohru
    Diet-induced obesity induces chronic inflammation. At postplandial period, various external antigens other than dietary lipids get into lymph ducts and evoke immune responses. In this study, we evaluated factors in lymph ducts by using lymph-cannulated rats especially at a postplandial period. At several hours after administration of dietary lipids, there was a significant increase of interleukin-6(IL-6) and glucagon-like peptide-1 in the lymph. Gene expression analysis in food-deprived or fed rats indicated that an accumulation of IL-6 producing cells in the intestinal mucosa accompanied by lipid absorption.
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 24658114
  • Enhancement of dietary peptide-induced GLP-1 secretion by indigestible saccharides
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    01 Apr. 2010 - 31 Mar. 2013
    HARA Hiroshi; HIRA Tohru
    GLP-1 is one of gastrointestinal hormones, and it has potent anti-obese and anti-diabetic effects. In the present project, we investigated whether indigestible peptides or indigestible saccharides are effective to increase GLP-1 secretion in a cell culture model and animal models. We also examined combined effects of indigestible saccharides and a dietary peptide.
    We demonstrated that oral administration of a dietary peptide (corn peptide) potently stimulated GLP-1 secretion and it resulted in reduced glycemic response in normal and diabetic rats.
    Luminal and oral administration of an indigestible saccharide (resistant maltodextrin, RMD) stimulated GLP-1 secretion in rats, and continuous ingestion of RMD also enhanced basal GLP-1 secretion. Furthermore, rats continuously having RMD showed increased GLP-1 secretory response to oral administration the corn peptide. These results revealed potential and combined effects of indigestible saccharides and dietary peptides in vivo.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 22380070
  • Searching for dietary protein/peptide sensing receptors in enteroendocrine cells
    Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    2011 - 2012
    HIRA Tohru
    We searched sensor molecules involved in dietary protein/peptide-sensing in enteroendocrine cells. By using enteroendocrine cell models, we found that a TRP channel was highly expressed in CCK-producing cell line.
    It was demonstrated that the TRP channel is involved in alpha-casein-induced CCK secretion. Furthermore, an aldehyde was found to induce CCK secretion through the TRP channel. Oral administration of the aldehyde reduced gastric emptying rate in rats, suggesting the aldehyde directly acts enteroendocrine cell and reduces gastric emptying in vivo.
    In separated experiments, we found that calcium-sensing receptor functions as sensor for various protein hydrolysates, rather than for specific peptides.
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, Principal investigator, Competitive research funding, 23780124
  • Role of CaSR as dietary peptide sensor and search for dietary protein receptor in the gut
    Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    2009 - 2010
    HIRA Tohru
    In this research project, we have investigated the function of calcium-sensing receptor (CaSR) as the receptor for luminal dietary peptides in gastrointestinal endocrine cells. Secretions of a gut hormone CCK induced by various dietary peptides were partially inhibited by the presence of CaSR antagonists. CaSR-expressing kidney cells also responded to various dietary peptides. These results suggest that CaSR is one of the receptor for dietary peptides in the gastrointestinal tract.
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, Principal investigator, Competitive research funding, 21780118
  • Development of anti-obese dietary peptides which functions via gut hormone secretion
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    2007 - 2009
    HARA Hiroshi; HIRA Tohru
    From various dietary peptides, we found that country bean peptide and beer yeast peptide have potent activity to stimulate a satiating gut hormone CCK in enteroeondcrine cell line. Oral preload of beer yeast peptide reduced following food consumption in rats. We also found that a hydrolysate prepared from corn protein Zein stimulates another gut hormone GLP-1. Ileal administration of Zein hydrolysate strongly induced GLP-1 secretion and subsequent insulin secretion in awake rats, which results in the improvement of glucose tolerance. These findings have revealed that dietary peptides are promising factor for prevention of overeating and hyperglycemia via stimulating gut hormone secretions.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 19380071
  • 食品タンパク質中の満腹感促進ペプチドの探索と消化管内分泌細胞におけるその受容機構
    科学研究費助成事業 若手研究(B)
    2005 - 2006
    比良 徹
    昨年度の研究において、フジ豆(ツル豆)より調製したペプトン(フジ豆ペプトン)に、食欲抑制作用を有する消化管ホルモンコレシストキニン(CCK)の分泌を強く刺激する活性があることを見いだした。このペプトンが由来するタンパクを明らかにするため、フジ豆たんぱくを等電点沈殿により分画し、各フラクションよりペプトンを調製して、CCK放出活性を調べたところ、等電点5にて沈殿する画分由来のペプトンに強い活性が見られた。この画分には分子量50kDa程のフジ豆の主要タンパクが多く含まれており、プロテインシークエンサーを使ったN末端アミノ酸配列の解析により、Phaseolin様のタンパクであった。Phaseolin由来のペプチドに強いCCK放出活性があることが示唆された。
    これまでの研究においてCCK産生細胞株STC-1からのCCK放出を刺激することが明らかとなったα-カゼインをリガンドとして、アフィニティー樹脂を用い、CCK産生細胞株STC-1の膜可溶化成分より、種々のα-カゼイン結合タンパクを分離した。プロテインシークエンサーにより解読できた一部のタンパクのアミノ酸配列は、インテグリン、オーファンGPCRと相同性を持っていたことから、これらの分子がα-カゼイン受容体である可能性が考えられた。
    また、STC-1細胞における細胞内情報伝達経路の解析により、この細胞のα-カゼイン認識において、Gαsタンパクが関与すること、ナトリウムチャネルを介した脱分極により細胞内カルシウムシグナルが惹起されることが明らかとなった。上記の受容体候補との関係を今後検討する。
    日本学術振興会, 若手研究(B), 北海道大学, Principal investigator, Competitive research funding, 17780097
  • 消化管における未知の食品タンパク質受容体の検索
    科学研究費助成事業 特別研究員奨励費
    2000 - 2002
    比良 徹
    昨年度までにマウス小腸由来の内分泌細胞株STC・1において、カゼインが細胞内カルシウム濃度上昇を引き起こすことを見出した。そのカルシウムの供給源を検討するため、L型カルシウムチャネルブロッカーDiltiazemの影響を調べた。Diltiazemで前処理されたSTC・1細胞において、α・カゼインによる細胞内カルシウム濃度上昇は有意に抑制され、このことから消化管内分泌細胞はα-カゼインを認識して細胞外からカルシウムを導入していることが示唆された。
    タンパク質上のグアニジル基が消化管で認識されることを示唆する結果をもとに、グアニジル基を有するアミノ酸であるホモアルギニンの投与に対する膵臓外分泌機能の応答を検討した。高コレシストキニン(CCK))血症のモデルとして使われる胆膵液除去ラットおよび正常ラットを外科手術により作製し、1週間の回復期間後にホモアルギニン溶液(10mg/rat)を投与し、投与前後の胆膵液を採取して膵酵素分泌を観察した。十二指腸へのホモアルギニン投与は両ラットに有意な変化を引き起こさなかったが、腹腔へのホモアルギニン投与により胆膵液除去ラットにおいてのみ、膵外分泌抑制作用が見られた。胆膵液除去ラットでのホモアルギニン長期投与の影響を調べるため、25%カゼイン、45%カゼイン、45%カゼイン+ホモアルギニン(19g/kg diet)を含む飼料を4日間与えたところ、45%カゼイン食により誘導された膵臓重量、膵酵素含量の増加は、ホモアルギニン添加により抑制された。胆膵液除去ラットにおける膵酵素の基礎分泌レベルの上昇および、高タンパク質食摂取による膵外分泌機能更新は血中CCK濃度上昇が関与すると考えられているので、ホモアルギニンは胆膵液除去および高タンパク質食により上昇したCCKの作用を血中で阻害する作用を持つこと、即ちCCKレセプターアンタゴニストとしての作用を持つことが示唆された。
    日本学術振興会, 特別研究員奨励費, 北海道大学, 00J06657
  • 消化管における栄養素認識機構
    Competitive research funding
  • Nutirent sensing mechanism in the gut
    Competitive research funding
■ Industrial Property Rights
  • GLP-1分泌促進剤
    Patent right, 矢田 俊彦; 岩崎 有作; 原 博; 比良 徹; 岸本 由香; 南 真知子, 学校法人自治医科大学, 国立大学法人北海道大学, 松谷化学工業株式会社
    特願2017-530931, 29 Jul. 2016
    特開2010-138143, 24 Jun. 2010
    特許第6896247号
    202103004169059868
  • GLP-1分泌促進剤及び組成物
    Patent right, 比良 徹; 原 博; 小松 陽介; 和泉 裕久, 森永乳業株式会社
    JP2018007005, 26 Feb. 2018
    WO2018-159546, 07 Sep. 2018
    202003005757708812
  • 過剰エネルギー摂取抑制用組成物
    Patent right, 比良 徹; 原 博; 名倉 泰三; 高橋 敬典; 奥原 康英; 石川 純嗣, 国立大学法人北海道大学, 日本甜菜製糖株式会社, 株式会社ファンケル
    特願2017-019582, 06 Feb. 2017
    特開2018-039776, 15 Mar. 2018
    201803007704700121
  • GLP-1分泌促進用組成物、及び該組成物の製造方法
    Patent right, 比良 徹; 原 博; 藤井 幹夫, 亀田製菓株式会社, 国立大学法人北海道大学
    特願2016-095639, 11 May 2016
    特開2017-203002, 16 Nov. 2017
    特許第6977945号
    201703015130502607
  • GLP-1分泌促進剤
    Patent right, 矢田 俊彦; 岩崎 有作; 原 博; 比良 徹; 岸本 由香; 南 真知子, 学校法人自治医科大学, 国立大学法人北海道大学, 松谷化学工業株式会社
    JP2016072269, 29 Jul. 2016
    WO2017-018500, 02 Feb. 2017
    WO2017-018500, 02 Feb. 2017
    201803003241411782
  • TRPA1活性化組成物
    Patent right, 比良 徹; 原 博; 西山 千草; 山下 貴稔; 今義 潤, 株式会社J-オイルミルズ
    特願2013-030850, 20 Feb. 2013
    特開2015-231953, 24 Dec. 2015
    特許第6077331号
    20 Jan. 2017
    201703020704050983
  • コレシストキニン分泌促進組成物
    Patent right, 原 博; 比良 徹; 西山 千草; 土倉 則子; 山下 貴稔; 今義 潤, 株式会社J-オイルミルズ
    特願2012-202450, 14 Sep. 2012
    特開2015-178459, 08 Oct. 2015
    特許第5951426号
    17 Jun. 2016
    201603003574652790
  • TRPA1活性化組成物
    Patent right, 比良 徹; 原 博; 西山 千草; 山下 貴稔; 今義 潤, 株式会社J-オイルミルズ, 国立大学法人北海道大学
    特願2013-030850, 20 Feb. 2013
    特開2015-231953, 24 Dec. 2015
    201603008520388666
  • コレシストキニン分泌促進組成物
    Patent right, 原 博; 比良 徹; 西山 千草; 土倉 則子; 山下 貴稔; 今義 潤, 株式会社J-オイルミルズ, 国立大学法人北海道大学
    特願2012-202450, 14 Sep. 2012
    特開2015-178459, 08 Oct. 2015
    201503012181907950
  • グルカゴン様ペプチド-1分泌促進剤
    Patent right, 鍔田 仁人; 原 博; 比良 徹, 株式会社東洋新薬, 国立大学法人北海道大学
    特願2011-133898, 16 Jun. 2011
    特開2012-020993, 02 Feb. 2012
    特許第5794678号
    21 Aug. 2015
    201503019720031422
  • グルカゴン様ペプチド-1分泌促進剤
    Patent right, 鍔田 仁人; 原 博; 比良 徹, 株式会社東洋新薬, 国立大学法人北海道大学
    特願2011-544281, 02 Dec. 2010
    特許第5721232号
    03 Apr. 2015
    201503090086819696
  • コレシストキニン分泌促進剤
    Patent right, 鍔田 仁人; 原 博; 比良 徹, 株式会社東洋新薬, 国立大学法人北海道大学
    特願2011-544280, 02 Dec. 2010
    特許第5674047号
    09 Jan. 2015
    201503084512039326
  • コレシストキニン分泌促進組成物
    Patent right, 原 博; 比良 徹; 西山 千草; 土倉 則子; 山下 貴稔; 今義 潤, 株式会社J-オイルミルズ
    JP2013068827, 10 Jul. 2013
    WO2014-041885, 20 Mar. 2014
    WO2014-041885, 20 Mar. 2014
    201603018851889814
  • 経口投与により食欲を抑制する素材
    Patent right, 原 博; 比良 徹; 池田 潔昭; 市原 敬司; 若村 香菜子, グリコハム株式会社, 国立大学法人北海道大学
    特願2011-226782, 14 Oct. 2011
    特開2013-082658, 09 May 2013
    201303078826848232
  • 糖尿病又は肥満病の予防又は治療剤
    Patent right, 原 博; 比良 徹; 江藤 譲; 安田 礼子, 味の素株式会社, 国立大学法人北海道大学
    特願2009-193368, 24 Aug. 2009
    特開2012-224547, 15 Nov. 2012
    201203001944681210
  • 摂食抑制作用を有する豚肉由来ペプチドを含有する組成物
    Patent right, 比良 徹; 原 博; 浅野 行蔵, 国立大学法人北海道大学
    特願2006-058172, 03 Mar. 2006
    特開2007-230978, 13 Sep. 2007
    特許第4929455号
    24 Feb. 2012
    201303023022744710
  • グルカゴン様ペプチド−1分泌促進剤
    Patent right, 鍔田 仁人; 原 博; 比良 徹, 株式会社東洋新薬, 国立大学法人北海道大学
    特願2011-133898, 16 Jun. 2011
    特開2012-020993, 02 Feb. 2012
    201203018386818743
  • 血中ジペプチジルペプチダーゼ−IV阻害活性およびグルカゴン様ペプチド−1の分泌促進活性を併せ持つ組成物
    Patent right, 原 博; 比良 徹; 浅野 行蔵, 浅野 行蔵
    特願2010-053383, 10 Mar. 2010
    特開2011-182742, 22 Sep. 2011
    201103016347682524
  • コレシストキニン分泌促進剤
    Patent right, 鍔田 仁人; 原 博; 比良 徹, 株式会社東洋新薬, 国立大学法人北海道大学
    JP2010071554, 02 Dec. 2010
    WO2011-068149, 09 Jun. 2011
    201303013576442141
  • グルカゴン様ペプチド−1分泌促進剤
    Patent right, 鍔田 仁人; 原 博; 比良 徹, 株式会社東洋新薬, 国立大学法人北海道大学
    JP2010071555, 02 Dec. 2010
    WO2011-068150, 09 Jun. 2011
    201303098218118869
  • 糖尿病又は肥満病の予防又は治療剤
    Patent right, 原 博; 比良 徹; 江藤 譲, 味の素株式会社, 国立大学法人北海道大学
    JP2009053409, 25 Feb. 2009
    WO2009-107660, 03 Sep. 2009
    201103074012143866
  • 摂食抑制作用を有する豚肉由来ペプチドを含有する組成物
    Patent right, 比良 徹; 原 博; 浅野 行蔵, 国立大学法人 北海道大学
    特願2006-058172, 03 Mar. 2006
    特開2007-230978, 13 Sep. 2007
    200903032408045880
  • 摂食抑制作用を有するペプチドを含有する組成物
    Patent right, 比良 徹; 廣塚 元彦; 中森 俊宏; 原 博; 浅野 行蔵; 千葉 仁志; 冨田 房男, 有限会社A−HITBio, 国立大学法人 北海道大学, 不二製油株式会社
    JP2006311426, 07 Jun. 2006
    WO2006-132273, 14 Dec. 2006
    200903047179049769

Research Profiles

■ Research Profiles