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研究者情報

マスター

アカウント（マスター）

  • 氏名

    加藤　英介(カトウ　エイスケ), カトウ　エイスケ

所属（マスター）

  • 農学研究院　基盤研究部門　生物機能化学分野

所属（マスター）

  • 農学研究院　基盤研究部門　生物機能化学分野

独自項目

syllabus

  • 2021, 大学院共通授業科目（一般科目）：自然科学・応用科学, Inter-Graduate School Classes(General Subject):Natural and Applied Sciences, 修士課程, 大学院共通科目, 食品、消化管、食品機能、腸内細菌叢、生理活性
  • 2021, 食品科学特論, Advanced Review of Food Science, 修士課程, 農学院, 食品、消化管、食品機能、腸内細菌叢、生理活性
  • 2021, 食品科学特論演習, Advanced Seminar on Food Science, 修士課程, 農学院, 食品、消化管、食品機能、腸内細菌叢、生理活性
  • 2021, 有機化学Ⅱ, Organic Chemistry II, 学士課程, 農学部, 芳?族化合物、カルボニル化合物、カルボン酸、アミン、求電子置換反応、求核付加反応、求核置換反応
  • 2021, 食品機能化学Ⅱ, Food Biochemistry II, 学士課程, 農学部, 食品、?品成分、健康機能、特定保健用?品、機能性表示食品、ポリフェノール、味覚
  • 2021, 化学実験Ⅱ, Laboratry Work on Chemistry II, 学士課程, 農学部, 食品成分、ポリフェノール、抗酸化物質、糖質消化酵素阻害物質、クロマトグラフィー、細胞培養

researchmap

プロフィール情報

学位

  • 博士（理学）（2007年03月 東北大学）

プロフィール情報

  • プロフィール

    天然物有機化学、有機合成化学などを利用した薬や健康食品のもととなる生物活性物質の探索や創造、作用機構解析をメインテーマとしています。現在、味覚受容体に関する研究に徐々にシフト中です。

  • 姓

    加藤, カトウ

  • 名

    英介, エイスケ

  • ID各種

    201301093124422719

対象リソース

業績リスト

研究キーワード

  • 苦味受容体   肥満   糖尿病   酵素阻害剤   

研究分野

  • ライフサイエンス / 食品科学
  • ライフサイエンス / 生物有機化学

経歴

  • 2020年07月 - 現在 北海道大学 大学院農学研究院 准教授
  • 2016年01月 - 2020年06月 北海道大学大学院農学研究院 講師
  • 2007年09月 - 2015年12月 北海道大学 大学院農学研究院 助教

学歴

  • 2004年04月 - 2007年03月   東北大学   大学院理学研究科   化学専攻
  • 2002年04月 - 2004年03月   慶應義塾大学   大学院理工学研究科
  • 1998年04月 - 2002年03月   慶應義塾大学   理工学部   化学科

委員歴

  • 2022年05月 - 現在   公益社団法人日本農芸化学会   北海道支部幹事
  • - 現在   公益社団法人日本化学会   代表正会員

受賞

  • 2018年03月 公益社団法人日本農芸化学会 農芸化学奨励賞
     食用植物の抗肥満、抗糖尿病効果を分子レベルで理解するための生物活性成分の探索と機能解析 
    受賞者: 加藤英介

論文

  • Eisuke Kato, Yosuke Inagaki, Hiromi Kayooka, Yusuke Adachi, Tomoaki Nagase, Naofumi Terada, Ai Tsuruma
    ACS Food Science & Technology 4 5 1209 - 1215 2024年05月17日 [査読有り][通常論文]
  • Saki Igarashi, Sayaka Hioki, Naoto Sakamaru, Asahi Suzuki, Mihoko Kurokawa, Eisuke Kato
    Natural Product Research 2024年04月12日
  • Naofumi Terada, Tomoaki Nagase, Hiromi Kayooka, Yusuke Adachi, Eisuke Kato
    Bioscience, Biotechnology, and Biochemistry 88 2 189 - 195 2024年01月24日 [査読有り][通常論文]
  • Eisuke Kato, Shota Oshima
    Receptors 2023年12月05日 [査読有り]
  • Fumina Ohsaka, Mayuko Yamaguchi, Yuka Teshigahara, Moeka Yasui, Eisuke Kato, Kei Sonoyama
    Biochemical and Biophysical Research Communications 685 149184 - 149184 2023年12月
  • Shunsuke Kimura, Ai Tsuruma, Eisuke Kato
    International Journal of Molecular Sciences 23 15 8120 - 8120 2022年07月23日 [査読有り][通常論文]
     
    Expression of taste 2 receptor (T2R) genes, also known as bitter taste receptor genes, has been reported in a variety of tissues. The white adipose tissue of mice has been shown to express Tas2r108, Tas2r126, Tas2r135, Tas2r137, and Tas2r143, but the function of T2Rs in adipocytes remains unclear. Here, we show that fasting and stimulation by bitter compounds both increased Tas2r expression in mouse white adipose tissue, and serum starvation and stimulation by bitter compounds both increased the expression of Tas2r genes in 3T3-L1 adipocytes, suggesting that T2Rs have functional roles in adipocytes. RNA sequencing analysis of 3T3-L1 adipocytes stimulated by epicatechin, the ligand of Tas2r126, suggested that this receptor may play a role in the differentiation of adipocytes. Overexpression of Tas2r126 in 3T3-L1 preadipocytes decreases fat accumulation after induction of differentiation and reduces the expression of adipogenic genes. Together, these results indicate that Tas2r126 may be involved in adipocyte differentiation.
  • Zhao Zhuoyue, Wijitrapha Ruangaram, Eisuke Kato
    Journal of Natural Medicines 75 4 1005 - 1013 2021年09月21日 [査読有り][通常論文]
  • Eisuke Kato, Ai Tsuruma, Ayaka Amishima, Hiroshi Satoh
    Bioscience, Biotechnology, and Biochemistry 85 8 1885 - 1889 2021年07月23日 [査読有り][通常論文]
     
    ABSTRACT Young barley leaves (Hordeum vulgare L.) have various health effects and are employed as an ingredient in the production of health-promoting foods. Promoting antiobesity is one such health effect; however, the mechanism and bioactive compounds are unclear. In this research, young barley leaf extract (YB) was demonstrated to possess pancreatic lipase inhibitory activity. The addition of YB to a high-fat diet in mice increased fecal lipid content, indicating reduced absorption of lipids as the mechanism underlying antiobesity effect. The investigation of bioactive compounds in YB resulted in the identification of fructose–bisphosphate aldolase as a proteinous lipase inhibitor. Maximum inhibition of the protein was 45%, but inhibition was displayed at a concentration as low as 16 ng/mL, which is a characteristic inhibition compared with other reported proteinous lipase inhibitors.
  • Maria Dewi P. Tirtaningtyas Gunawan-Puteri, Eisuke Kato, Della Rahmawati, Stevan Teji, Jevon Ardy Santoso, Febbyandi Isnanda Pandiangan, Yanetri Asi Nion
    International Journal of Technology 12 3 649 - 649 2021年07月19日 [査読有り][通常論文]
  • Eisuke Kato
    Gene Reports 20 100763 - 100763 2020年09月 [査読有り][通常論文]
  • Wijitrapha Ruangaram, Eisuke Kato
    Pharmaceuticals 13 4 56 - 56 2020年03月29日 [査読有り][通常論文]
     
    The prevalence of obesity is increasing globally. Despite the availability of a variety of anti-obesogenic drugs, including therapies under clinical development, these treatments are often indicated for patients with severe obesity, making them unsuitable for patients with mild obesity or for preventative use. In Thailand, traditional remedies employing medicinal plants are widely used to maintain health and treat disease. These treatments are generally inexpensive and readily available at markets, making them good treatment options for preventing obesity. To evaluate the anti-obesogenic potential of Thai medicinal plants, we employed three in vitro methods: pancreatic lipase inhibition, lipolysis enhancement, and lipid accumulation reduction assays. Among 70 Thai medicinal plants, Eurycoma longifolia Jack, Tiliacora triandra Diels, and Acacia concinna (Willd.) DC. were selected as the most favorable candidates because they exhibited anti-obesogenic activity in all three assays. These medicinal plants are expected to have efficient anti-obesogenic effects, making them promising candidates for further study.
  • Eisuke Kato, Natsuka Kushibiki, Hiroshi Satoh, Jun Kawabata
    Natural Product Research 34 6 759 - 765 2020年03月18日 [査読有り][通常論文]
  • Lucy Lahrita, Kenta Moriai, Ryohei Iwata, Kazuki Itoh, Eisuke Kato
    Fitoterapia 137 104250 - 104250 2019年09月 [査読有り][通常論文]
  • Eisuke Kato
    Bioscience, Biotechnology, and Biochemistry 83 6 975 - 985 2019年06月03日 [査読有り][招待有り]
     
    ABSTRACT Plant materials have been widely studied for their preventive and therapeutic effects for type 2 diabetes mellitus (T2DM) and obesity. The effect of a plant material arises from its constituents, and the study of these bioactive compounds is important to achieve a deeper understanding of its effect at the molecular level. In particular, the study of the effects of such bioactive compounds on various biological processes, from digestion to cellular responses, is required to fully understand the overall effects of plant materials in these health contexts. In this review, I summarize the bioactive compounds we have recently studied in our research group that target digestive enzymes, dipeptidyl peptidase-4, myocyte glucose uptake, and lipid accumulation in adipocytes. Abbreviations: AC: adenylyl cyclase; AMPK: AMP-activated protein kinase; βAR: β-adrenergic receptor; CA: catecholamine; cAMP: cyclic adenosine monophosphate; cGMP: cyclic guanosine monophosphate; DPP-4: dipeptidyl peptidase-4; ERK: extracellular signal-regulated kinase; GC: guanylyl cyclase; GH: growth hormone; GLP-1: glucagon-like peptide-1; GLUT: glucose transporter; HSL: hormone-sensitive lipase; IR: insulin receptor; IRS: insulin receptor substrate; MAPK: mitogen-activated protein kinase; MEK: MAPK/ERK kinase; MG: maltase-glucoamylase; NP: natriuretic peptide; NPR: natriuretic peptide receptor; mTORC2: mechanistic target of rapamycin complex-2; PC: proanthocyanidin; PI3K: phosphoinositide 3-kinase; PKA: cAMP-dependent protein kinase; PKB (AKT): protein kinase B; PKG: cGMP-dependent protein kinase; PPARγ: peroxisome proliferator-activated receptor-γ; SGLT1: sodium-dependent glucose transporter 1; SI: sucrase-isomaltase; T2DM: type 2 diabetes mellitus; TNFα: tumor necrosis factor-α.
  • Eisuke Kato, Kazuhiro Kawakami, Jun Kawabata
    Journal of Enzyme Inhibition and Medicinal Chemistry 33 1 106 - 109 2018年01月01日 [査読有り][通常論文]
  • Eisuke Kato, Shunsuke Kimura, Jun Kawabata
    BIOORGANIC & MEDICINAL CHEMISTRY 25 24 6412 - 6416 2017年12月 [査読有り][通常論文]
     
    beta 2-Adrenergic receptor (beta 2AR) agonists are employed as bronchodilators to treat pulmonary disorders, but are attracting attention for their modulation of glucose handling and energy expenditure. Higenamine is a tetrahydroisoquinoline present in several plant species and has beta 2AR agonist activity, but the involvement of each functional groups in beta 2AR agonist activity and its effectiveness compared with endogenous catecholamines (dopamine, epinephrine, and norepinephrine) has rarely been studied. Glucose uptake of muscle cells are known to be induced through beta 2AR activation. Here, the ability to enhance glucose uptake of higenamine was compared with that of several methylated derivatives of higenamine or endogenous catecholamines. We found that: (i) the functional groups of higenamine except for the 40-hydroxy group are required to enhance glucose uptake; (ii) higenamine shows a comparable ability to enhance glucose uptake with that of epinephrine and norepinephrine; (iii) the S-isomer shows a greater ability to enhance glucose uptake compared with that of the R-isomer. (C) 2017 Elsevier Ltd. All rights reserved.
  • Kato Eisuke, Iwata Ryohei, Kawabata Jun
    Molecules 22 9 1450  2017年09月 [査読有り][通常論文]
     
    Higenamine is a tetrahydroisoquinoline present in several plants that has β-adrenergic receptor agonist activity. Study of the biosynthesis of higenamine has shown the participation of norcoclaurine synthase, which controls the stereochemistry to construct the (S)-isomer. However, when isolated from nature, higenamine is found as the racemate, or even the (R)-isomer. We recently reported the isolation of higenamine 4′-O-β-d-glucoside. Herein, its (R)- and (S)-isomers were synthesized and compared to precisely determine the stereochemistry of the isolate. Owing to their similar spectral properties, determination of the stereochemistry based on NMR data was considered inappropriate. Therefore, a high-performance liquid chromatography method was established to separate the isomers, and natural higenamine 4′-O-β-d-glucoside was determined to be a mixture of isomers.
  • Lucy Lahrita, Ryota Hirosawa, Eisuke Kato, Jun Kawabata
    BIOORGANIC & MEDICINAL CHEMISTRY 25 17 4829 - 4834 2017年09月 [査読有り][通常論文]
     
    Eurycomanone (1) and 13 beta,21-epoxyeurycomanone (2) were isolated from Eurycoma longifolia for studies of lipolytic activity. Compound 1 enhanced lipolysis in adipocytes with an EC50 of 14.6 M, while its epoxy derivate, compound 2, had a stronger activity with an EC50 of 8.6 M. Based on molecular mechanistic study using several specific inhibitors to lipolytic signaling pathways, it was found that PKA inhibitor totally diminished the lipolytic activity of 1 and 2. Further immunoblotting analysis confirmed the activation of phosphorylated PKA by both 1 and 2. With the growing need to develop new anti-obesity agents, eurycomanone and its epoxy derivate can be used as promising lead compounds to target lipid catabolism. (C) 2017 Elsevier Ltd. All rights reserved.
  • Noda Kota, Kato Eisuke, Kawabata Jun
    Natural Product Communications 12 8 1259 - 1261 2017年08月 [査読有り][通常論文]
     
    Achillea millefolium is a plant used as a component of anti-diabetic preparation but the bioactive compounds responsible for its use are not known. Inhibition of intestinal alpha-glucosidase is a preferable effect for prevention and treatment of diabetes, and A. millefolium extract showed inhibitory activity against the enzyme. Activity-guided separation of the extract gave four mono- or di-caffeoylquinic acids as the isolate. Quantitation of these four caffeoylquinic acids and the activity of the isolates suggested that these are the major contributor for the alpha-glucosidase inhibitory activity in the extract. However also, the presence of unidentified, minor, but potent alpha-glucosidase inhibitor in the isolate was also suggested.
  • Eisuke Kato, Natsuka Kushibiki, Yosuke Inagaki, Mihoko Kurokawa, Jun Kawabata
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 81 9 1699 - 1705 2017年 [査読有り][通常論文]
     
    Type 2 diabetes mellitus (T2DM) is a common global health problem. Prevention of this disease is an important task, and functional food supplements are considered an effective method. We found potent pancreatic -amylase inhibition in Astilbe thunbergii root extract (AT) and confirmed that AT treatment in a T2DM rat model reduces post-starch administration blood glucose levels. Activity-guided isolation revealed procyanidin (AT-P) as the -amylase inhibitory component with IC50=1.7g/mL against porcine pancreatic -amylase. Structure analysis of AT-P revealed it is a B-type procyanidin comprised of four types of flavan-3-ols, some with a galloyl group, and catechin attached as the terminal unit. The abundant AT-P content and its comparable -amylase inhibition to acarbose, the anti-diabetic medicine, suggest that AT is a promising food supplement for diabetes prevention.
  • Eisuke Kato, Fumiaki Chikahisa, Jun Kawabata
    Tetrahedron Letters 57 12 1365 - 1367 Elsevier {BV} 2016年03月 [査読有り][通常論文]
     
    Pancreatic alpha-amylase is a target for type 2 diabetes mellitus treatment. However, small molecule inhibitors of alpha-amylase are currently scarce. In the course of developing small molecule alpha-amylase inhibitors, we designed and synthesized conjugates of glucose and acarviosin. The synthetic compounds showed mild alpha-amylase inhibitory activity with higher activity compared with non-glucose conjugated compounds, but lower activity compared to acarviosin. Comparison of these activities revealed transglycosylation of acarviosin during the enzyme reaction. Additionally, the alpha-amylase inhibitory activity of acarviosin is expressed through these transglycosylation products. (C) 2016 Elsevier Ltd. All rights reserved.
  • Eisuke Kato, Yuta Uenishi, Yosuke Inagaki, Mihoko Kurokawa, Jun Kawabata
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 80 11 2087 - 2092 2016年 [査読有り][通常論文]
     
    Dipeptidyl peptidase-IV (DPP-IV) is a protease responsible for the degradation of the incretin hormone. A number of DPP-IV inhibitors have been approved for use in the treatment of type 2 diabetes. While these inhibitors are effective for this treatment, methods for the prevention of this disease are also required as diabetes patient numbers are currently increasing rapidly worldwide. We screened the DPP-IV inhibitory activities of edible plant extracts with the intention of using these extracts in a functional food supplement for the prevention of diabetes. Rose (Rosa gallica) bud extract powder was a promising material with high inhibitory activity. In this study, seven ellagitannins were isolated as active compounds through activity-guided fractionations, and their DPP-IV inhibitory activities were measured. Among them, rugosin A and B showed the highest inhibitory activities and rugosin B was shown as the major contributing compound in rose bud extract powder.
  • Eisuke Kato, Yosuke Inagaki, Jun Kawabata
    Bioorganic {\&} Medicinal Chemistry 23 13 3317 - 3321 Elsevier {BV} 2015年07月 [査読有り][通常論文]
     
    Hypoglycemic effect is an efficient means to modulate elevated blood glucose levels in patients with diabetes. We found that the extract of lotus plumule (the germ of Nelumbo nucifera Gaertn. seed) showed potent glucose uptake enhancement activity against L6 myotubes, which results in a hypoglycemic effect. This activity was further investigated, and an active constituent was identified as a single bioactive compound, higenamine 4'-O-beta-D-glucoside. Mechanistic studies employing phosphatidylinositol 3-kinase (PI3K) inhibitor, AMP-activated protein kinase (AMPK) inhibitor, or adrenergic receptor antagonist showed that the compound induced its activity through beta 2-adrenergic receptor. Patients with type II diabetes mellitus frequently develop insulin resistance. Owing to the differences between the mechanism of action of insulin and of the isolated compound, the compound or lotus plumule itself may have the possibility of modulating blood glucose levels in insulin-resistant patients effectively. (C) 2015 Elsevier Ltd. All rights reserved.
  • Lucy Lahrita, Eisuke Kato, Jun Kawabata
    JOURNAL OF ETHNOPHARMACOLOGY 168 229 - 236 2015年06月 [査読有り][通常論文]
     
    Ethnopharmacological relevance: As obesity is a key factor in the development of type 2 diabetes, lowering lipid accumulation in adipose tissues is as important as increasing insulin sensitivity in diabetic patients. The selected plant extracts used in this screen have been traditionally used in Indonesian medicine for the treatment of diabetes and its complications. Aim of the study: To investigate the ability of the selected plants to both increase insulin sensitivity through the enhancement of glucose uptake after insulin induction in adipocytes and suppress lipid production in the same target cells. Materials and methods: Dried Indonesian medicinal plants were extracted with 50% (v/v) aq. methanol. The extracts were dissolved in 50% DMSO when tested in 3T3-L1 adipocytes. The screening platform consists of insulin-induced glucose uptake, lipid accumulation, and cell viability. Initially, an enzymatic fluorescence assay was designed to demonstrate the enhancement of 2-deoxyglucose (2-DG) uptake after insulin induction. Different concentrations of the extracts that enhanced glucose uptake were subjected to lipid accumulation assay using Oil Red 0 staining. Potential extracts based on lipid suppression were subsequently assessed by CCK-8 cell viability assay to distinguish lipid reduction activity from cytotoxicity. Results: Out of 59 plants, 13 plants demonstrated their ability to increase glucose uptake in 3T3-L1 adipocytes after insulin induction, and 4 of these plants' extracts suppressed lipid production of the cells. The CCK-8 assay results of those 4 plant extracts suggest that the lipid inhibition activity of Eurycoma longifolia Jack (root) and Piper nigrum L (fruits) extracts is not attributed to their cytotoxicity in the adipose cells. Both of the plant extracts increased glucose uptake by more than 200% at 50 mu g/mL and suppressed lipid accumulation in a concentration-dependent manner. Conclusions: Screening of selected Indonesian medicinal plants has uncovered the potentials of E. longifolia Jack (root) and P. nigrum L (fruits) with dual active functions, increasing insulin sensitivity through the enhancement of glucose uptake and reducing lipid accumulation in adipose cells. These findings suggest that the ability of both plants to suppress lipid production would provide additional benefits in the treatment of diabetes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Eisuke Kato, Hiroki Tsuji, Jun Kawabata
    TETRAHEDRON 71 9 1419 - 1424 2015年03月 [査読有り][通常論文]
     
    Affinity chromatography of specific enzymes is limited by the presence of related enzymes and the limited selectivity of the affinity ligand. We synthesized and investigated the use of an uncompetitive inhibitor as an affinity ligand, to leverage its three-component interactions. Use of the potent a-glucosidase uncompetitive inhibitor 2-aminoresorcinol as the ligand of the affinity gel offered selective purification of maltase-glucoamylase complex from the crude mixture of intestinal a-glucosidases. (C) 2015 Elsevier Ltd. All rights reserved.
  • Yonemoto R, Shimada M, Gunawan-Puteri M.D.P.T, Kato E, Kawabata J
    Journal of Agricultural and Food Chemistry 62 33 8411 - 8414 2014年08月 [査読有り][通常論文]
     
    In the screening experiments for porcine pancreatic a-amylase inhibitors in 18 plants obtained from Indonesia, a potent inhibitory activity was detected in the extract of leaves of Abrus precatorius. The enzyme assay-guided fractionation of the extract led to the isolation of a triterpene ketone, lupenone (1), as a potent alpha-amylase inhibitor, together with 24-methylenecycloartenone (2) and luteolin (3). The mode of inhibition of compound 1 against porcine pancreatic alpha-amylase was a mixed inhibition. This is the first report that describes the potent alpha-amylase inhibitory activity of the low-polar triterpene ketone similar to compound 1. A comparison of the activities of the isolate and related compounds indicated the importance of C-3 ketone and the lupane skeleton in the alpha-amylase inhibitory activity.
  • Taro Kimura, Eisuke Kato, Tsukasa Machikawa, Shunsuke Kimura, Shinji Katayama, Jun Kawabata
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 445 1 6 - 9 2014年02月 [査読有り][通常論文]
     
    Diabetes mellitus is a global disease, and the number of patients with it is increasing. Of various agents for treatment, those that directly act on muscle are currently attracting attention because muscle is one of the main tissues in the human body, and its metabolism is decreased in type II diabetes. In this study, we found that hydroxylamine (HA) enhances glucose uptake in C2C12 myotubes. Analysis of HA's mechanism revealed the involvement of IRS1, PI3 K and Akt that is related to the insulin signaling pathway. Further investigation about the activation mechanism of insulin receptor or IRS1 by HA may provide a way to develop a novel anti-diabetic agent alternating to insulin. (C) 2014 Elsevier Inc. All rights reserved.
  • Arsiningtyas I.S, Gunawan-Puteri M.D.P.T, Kato E, Kawabata J
    Natural Product Research 28 17 1350 - 1353 2014年 [査読有り][通常論文]
     
    A promising approach for treating diabetes mellitus (DM) is to decrease postprandial hyperglycaemia by suppressing carbohydrate digestion using a-glucosidase inhibitors. Pluchea indica leaf extracts possess inhibitory activity against intestinal maltase. Enzyme assay-guided fractionation by chromatography yielded five active caffeoylquinic acid derivatives (1-5). Their structures were elucidated by mass spectrometry and NMR analysis and completed by comparison with reference data. 3,5-Di-O-caffeoylquinic acid (1), 4,5-di-O-caffeoylquinic acid methyl ester (2), 3,4,5-tri-O-caffeoylquinic acid methyl ester (3), 3,4,5-tri-O-caffeoylquinic acid (4) and 1,3,4,5-tetra-O-caffeoylquinic acid (5) were isolated. Comparison of the activities of each isolate suggested that both methyl esterification of quinic acid and the number of caffeate groups in the molecule were important for the inhibitory activity. This study provides basic information for further examination of the suitability of P. indica as a functional food and medicinal supplement for the treatment and prevention of diabetes.
  • Eisuke Kato, Ryo Nakagomi, Maria D. P. T. Gunawan-Puteri, Jun Kawabata
    FOOD CHEMISTRY 136 3-4 1239 - 1242 2013年02月 [査読有り][通常論文]
     
    Inhibition of pancreatic lipase is effective for a prevention of obesity. Eugenia polyantha is a tropical tree whose leaves are known as a spice and also as an ingredient for Jamu, the traditional medicine of Indonesia. We found inhibitory activity against pancreatic lipase in the extract of E. polyantha leaves. Purification of the active principals resulted in isolation of hydroxychavicol, and two structurally new dimers. All of the isolated compounds showed inhibitory activity against the porcine pancreatic lipase and high content of hydroxychavicol (1.83 wt.%) indicated this compound to be responsible for the majority of inhibitory activity of E. polyantha extract. Furthermore, hydroxychavicol is reported to possess anti-carcinogenic, anti-oxidant, anti-microbial and anti-inflammatory activity which is related to traditional usage of this plant. These results offer this plant as an attractive material for treating various health problems including obesity. (C) 2012 Elsevier Ltd. All rights reserved.
  • Eisuke Kato, Michitsugu Yama, Ryo Nakagomi, Toshiro Shibata, Keizo Hosokawa, Jun Kawabata
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 22 20 6410 - 6412 2012年10月 [査読有り][通常論文]
     
    Filipendula kamtschatica is a plant utilized as a traditional medicine by Ainu people in Japan, but its chemical constituents are not much studied. Pancreatic lipase inhibitors are a promising tool for the treatment of obesity. We searched for natural lipase inhibitors from F. kamtschatica and two new compounds were isolated along with the known flavonoid glycoside. The structure elucidation of new compounds revealed these two to be 2-O-caffeoyl-4-O-galloyl-L-threonic acid and 3-O-caffeoyl-4-O-galloyl-L-threonic acid, which can be recognized as a pancreatic lipase's substrate-like structure. The isolated compounds all showed an inhibitory activity against porcine pancreatic lipase and one of the isomer, 3-O-caffeoyl-4-O-galloyl-L-threonic acid, possessed the most potent activity with IC50 value showing an order lower value compared to others. The substrate-like structure of the new compounds seemed to be important for their activity. (c) 2012 Elsevier Ltd. All rights reserved.
  • Eisuke Kato, Kenichi Oikawa, Keisuke Takahashi, Jun Kawabata
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 76 5 1044 - 1046 2012年05月 [査読有り][通常論文]
     
    2-Aminoresorcinol is a potent and selective intestinal glucosidase inhibitor. Unlike the majority of glucosidase inhibitors, it shows an uncompetitive mode of inhibition. In this study, we tested the intestinal glucosidase inhibitory activity of various 2-aminoresorcinol derivatives. We found that structural changes, in amino and two phenolic hydroxyl groups had a negative impact on inhibitory activity, but methylation of the phenolic hydroxyl group was found to maintain its activity and replacement of the aromatic ring with an acyl or alkoxy carbonyl group at the 4th position also retained its activity. This enable us to design a molecular probe for further study of the inhibition mechanism of 2-aminoresorcinol.
  • Kazuaki Yamasaki, Ryogo Hishiki, Eisuke Kato, Jun Kawabata
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 76 4 841 - 842 2012年04月 [査読有り][通常論文]
     
    Insulin mimetics are considered as prospective antidiabetic agents, and the disaccharide, neohesperidose, has been found to show insulin mimetic activity against L6 cells. We screened several other disaccharides for their insulin mimetic activity and identified three new insulin mimetic disaccharides.
  • Gunawan-Puteri M.D.P.T, Kato E, Kawabata J
    Journal of the Science of Food and Agriculture 92 3 606 - 609 2012年02月 [査読有り][通常論文]
     
    BACKGROUND: Diabetes mellitus and associated diseases are an increasing problem around the world. One of the hyperglycemic remedies is glucose absorption reduction by suppressing carbohydrate digestion due to utilization of alpha-amylase inhibitors. RESULTS: Prospective herbs were analyzed by in vitro enzyme assay to evaluate their inhibitory activity against porcine pancreatic amylase (PPA), and it was found that Phyllanthus urinaria and three other herbs to showed a potent inhibitory activity. A 50% aqueous methanol-soluble extract of the leaves of P. urinaria was chromatographed using a silica gel column. The active fractions were further purified by preparative high-performance liquid chromatography to isolate active principles against PPA. Structural determination revealed that these isolated compounds were gallic acid, corilagin, and macatannin B, and showed mild activity against PPA (activity in 1 mmol L(-1) concentration: 23%, 21%, 33%, respectively). CONCLUSION: P. urinaria extracts show inhibitory activity against PPA. This activity, together with the information on isolated compounds, may benefit further exploration of P. urinaria utilization in the management of borderline diabetes patients. (C) 2011 Society of Chemical Industry
  • Eisuke Kato, Naoya Iwano, Akihiko Yamada, Jun Kawabata
    TETRAHEDRON 67 40 7692 - 7702 2011年10月 [査読有り][通常論文]
     
    Inhibitors of alpha-amylase have attracted attention for their putative effects against diabetes mellitus. Although numerous studies have explored natural small molecule inhibitors, acarbose is currently the only compound with sufficient inhibitory potency and drug-like characteristics to be considered as a potential therapeutic agent. We have synthesized conjugates of the potent glucosidase inhibitor, 1-deoxynojirimycin, and glucose, with the aim of enhancing inhibitory activity against alpha-amylase. This synthetic conjugate showed increased inhibition of alpha-amylase compared to 1-deoxynojirimycin alone, suggesting that similar modifications of existing glucosidase inhibitors may yield more potent alpha-amylase inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.
  • Kazuaki Yamasaki, Ryogo Hishiki, Eisuke Kato, Jun Kawabata
    ACS MEDICINAL CHEMISTRY LETTERS 2 1 17 - 21 2011年01月 [査読有り][通常論文]
     
    Diabetes mellitus is increasing in prevalence with patient numbers rising throughout the world. Current treatments for-diabetes mellitus focus on control of blood glucose levels. Certain kinds of flavonoids or their glycosides stimulate cells to improve glucose uptake and lower blood glucose levels. We synthesized kaempferol 3-O-neohesperidoside (1) a naturally occurring substance present in Cyathea phalerata Mart., reported to mimic the action of insulin. Synthetic 1 promoted glucose uptake in the cultured cell line, L6. Further studies to determine the core structure responsible for this activity using synthetic compounds revealed neohesperidose to be the primary pharmacophore. These findings support the use of certain saccharides as a potential novel treatment for diabetes mellitus by replacing or supporting insulin.
  • 山崎 一諒, 飛鋪 亮吾, 加藤 英介, 川端 潤
    天然有機化合物討論会講演要旨集 52 409 - 414 天然有機化合物討論会 2010年09月01日 
    Diabetes mellitus (DM) is a currently arising disease with patients increasing throughout the world. Treaments of diabetes mellitus focus on control of blood glucose level. In late years, some of flavonoid glycosides are reported as an insulin-mimetic compound which regulates glucose uptake ability of insulin-sensitive cells (insulin-mimetic activity). These compounds are thought to be effective for the treatment of DM by replacing insulin or supporting currently used medicines. One of these insulin-mimetic flavonoid glycosides, kaempferol 3-O-neohesperidoside (1), was idolated from a stem of Cyathea phalerata Mart., and reported to show strong insulin-mimetic activity at nanomolar level. We focused on this attractive compound, and started to perform a structure-activity relationship study on the insulin-mimetic effect of 1 by a synthetic method and in vitro assay emloying cultured cells. We achieved a synthesis of 1 for the first time, and performed insluin-mimetic activity examination of synthetic 1 against muscular cell model. L6 cells. As a result, a significantly high activity was observed in synthetic 1 at 1 nM. Further study on structure-activity relationship using several synthetic derivatives with partial structure of 1 revealed that neohesperidose (19) to be the major contributing structure for this activity. These findings may lead to utilization of disacchrides for treatment for diabetes mellitus.
  • M. Gunawan-Puteri, E. Kato, J. Kawabata
    PLANTA MEDICA 76 12 1182 - 1182 2010年08月 [査読有り][通常論文]
  • Eisuke Kato, Jun Kawabata
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 20 15 4333 - 4336 2010年08月 [査読有り][通常論文]
     
    Chemical treatment of diabetes mellitus is widely studied and controlling of blood glucose level is the main course of therapy. In type 2 diabetes mellitus, insulin resistance is the major problem. An isoflavone C-glucoside, puerarin (1), is known to enhance glucose uptake into the insulin sensitive cell and is thought to be a candidate for treatment of diabetes mellitus. We synthesized 1 and several derivatives to apply for the structure-activity relationship study. The result against 3T3-L1 adipocyte indicated that the C-glucoside part of 1 is unconcerned in its activity when tested in vitro and the main structure responsible for its activity was the isoflavone moiety. (C) 2010 Elsevier Ltd. All rights reserved.
  • Keisuke Takahashi, Yasuyuki Yoshioka, Eisuke Kato, Shigeki Katsuki, Osamu Iida, Keizo Hosokawa, Jun Kawabata
    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 74 4 741 - 745 2010年04月 [査読有り][通常論文]
     
    In screening experiments for rat intestinal alpha-glucosidase (sucrase and maltase) inhibitors in 325 plants cultivated in Japan's southern island, of Tanegashima, marked inhibition against both sucrase and maltase was found in the extract of the fruit of Solanum torvum. Enzyme-assay guided fractionation of the extract led to the isolation of methyl caffeate (1) as a rat intestinal sucrase and maltase inhibitor. We examined 13 caffeoyl derivatives for sucrase- and maltase-inhibitory activities. The results showed that methyl caffeate (1) had a most favorable structure for both sucrase and maltase inhibition, except for a higher activity of methyl 3,4,5-trihydroxycinnamate (14) against sucrase. Its moderate inhibitory action against alpha-glucosidase provides a prospect for antidiabetic usage of S. torvum fruit.
  • Eisuke Kato, Takehiko Sasaki, Minoru Ueda
    BIOORGANIC & MEDICINAL CHEMISTRY 16 8 4600 - 4616 2008年04月 [査読有り][通常論文]
     
    The synthesis of an affinity gel aimed at leaf-opening factor beta-glucosidase (LOFG) and affinity purification of LOFG is presented. A gluconamidine-based beta-glucosidase inhibitor was used as the ligand of the affinity gel. beta-Glucosidase exhibiting an activity shift throughout the day was selectively purified from Lespedeza cuneata Don by the affinity gel. The resulting LOFG exhibited high substrate specificity toward the leaf-opening factor. (c) 2008 Elsevier Ltd. All rights reserved.
  • Eisuke Kato, Takehiko Sasaki, Tadahiro Kumagai, Minoru Ueda
    TETRAHEDRON LETTERS 48 13 2409 - 2413 2007年03月 [査読有り][通常論文]
     
    Synthesis of affinity get aimed for leaf-opening factor beta-glucosidase (LOFG) and affinity purification of LOFG are presented. Gluconamidine-based beta-glucosidase inhibitor was utilized for the ligand of the affinity gel. beta-Glucosidase exhibiting activity shift throughout the day was selectively purified from Lespedeza cuneata Don by the affinity gel. The resulting LOFG exhibited a high substrate specificity toward the leaf-opening factor. (c) 2007 Published by Elsevier Ltd.
  • Eisuke Kato, Rachel Howitt, Sergei V. Dzyuba, Koji Nakanishi
    ORGANIC & BIOMOLECULAR CHEMISTRY 5 23 3758 - 3761 2007年 [査読有り][通常論文]
     
    Site-selective introduction of biotin and benzophenone probes onto ginkgolide scaffolds is described.
  • M Ueda, T Fujii, E Kato, T Sugimoto, N Kato
    JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 64 2 117 - 129 2006年02月 [査読有り][通常論文]
     
    Circadian rhythmic plant leaf-movement, called nyctinasty, is controlled by a time-course change in the internal concentration of the leaf movement factors (leaf-opening and leaf-closing substances) in the plant body. We revealed that the target cell for the leaf-movement factors is plant motor cell by using novel synthetic fluorescence labeled probes. Using photoaffinity probes 21, the specific binding proteins for potassium lespedezate 1, the leaf-opening substance of Cassia mimosoides L, are detected from the plasma membrane fraction of the plant motor cell. Our study is a rare successful result of the detection of membrane receptors by using a synthetic photoaffinity probe designed on a biologicallly active natural product. These results also advance a guideline for probe design towards successful photoaffinity labeling. The balance of concentration of the leaf movement factors is inversed during the day. The glycoside type leaf movement factor is hydrolyzed with beta-glucosidase, the activity of which is regulated by the biological clock. The circadian rhythm observed in the leaf movement is introduced by activation of the beta-glucosidase regulated by the biological clock. We synthesized the glyconoamidine gel 43 designed on potassium lespedezate, a glycoside type leaf-opening substance, and succeeded in purification of the beta-glucosidase, a key enzyme of circadian rhythmic plant leaf-movement, by affinity chromatography using affinity gel 43.
  • Mitsuru Shoji, Eisuke Kato, Yoko Nakamura, Tomohiko Fujii, Yoshiyuki Manabe, Minoru Ueda
    CHEMICAL RECORD 6 6 344 - 355 2006年 [査読有り][通常論文]
     
    The chemical aspects of the circadian leaf movement known as "nyctinasty" are discussed in this paper. Each of the nyctinastic plants of five different genera so far examined contained a pair of factors, one of which induced leaf closure and another induced leaf opening. The relative contents of the closing and opening factors changed correlating with the nyctinastic leaf movement. The use of fluorescence-labeled and photoaffinity-labeled factors revealed that the factors bind to specific cells, the motor cells, present in the pulvini, and that the membrane fraction of the motor cells contained two proteins of 210 and 180 kDa, which can bind to the factors. (c) 2007 The Japan Chemical journal Forum and Wiley Periodicals, Inc.
  • E Kato, T Kumagai, M Ueda
    TETRAHEDRON LETTERS 46 29 4865 - 4869 2005年07月 [査読有り][通常論文]
     
    Glycosidases are involved in deactivation or storage of some endogenous bioactive substances through biologically intriguing processes. For example, nyetinastic leaf movement is controlled by a biological clock through the regulation of beta-glucosidase activity. Ganem's glyconoamidine (1) is used as a micromolar inhibitor of glucosidase in biochemical studies and would be useful as an affinity ligand for purification of glycosidase. However, its use for the specific inhibition of glucosidase which is highly specific to a glycoside with voluntary aglycon is seriously restricted because no universal method for the synthesis of N-alkylated glyconoamidine has been reported. Here, we report a concise synthesis of N-alkylated Ganem's glyconoamidine with voluntary aglycon using a non-protected sugar derivative. (c) 2005 Elsevier Ltd. All rights reserved.
  • E Kato, H Nagano, S Yamamura, M Ueda
    TETRAHEDRON 59 31 5909 - 5917 2003年07月 [査読有り][通常論文]
     
    Nyctinasty has been known since pre-Christian era, whereas the question 'Why do leguminous plants sleep?' has always puzzled scientists. This paper gives a clue to the historical mystery: by using synthetic inhibitors for nyctinasty, we found that legumes cannot survive without nyctinasty. (C) 2003 Elsevier Ltd. All rights reserved.
  • H Nagano, E Kato, S Yamamura, M Ueda
    TETRAHEDRON LETTERS 44 14 2953 - 2956 2003年03月 [査読有り][通常論文]
     
    We developed fluorescent probes (1 and 2) based on the structure of cis-p-coumaroylagmatine (3), a leaf-opening Substance of Albizzia julibrissim Durazz. These probes were effective for the leaf-opening of A. julibrissin, and specifically bind to the motor cell of this plant. Moreover, binding of the fluorescent probe was specific to the plant motor cell contained in the plants belonging to the Albizzia genus. These results showed that the binding of a probe compound with a motor cell is specific to the plant genus and suggested that the genus-specific receptor molecule Cor the leaf movement factor on a motor cell Would be involved in nyctinasty. (C) 2003 Elsevier Science Ltd. All rights reserved.
  • E. Kato, H. Nagano, S. Yamamura, M.Ueda
    Tetrahedron 59 31 5909 - 5917 2003年 [査読有り][通常論文]
  • H Nagano, E Kato, S Yamamura, M Ueda
    ORGANIC & BIOMOLECULAR CHEMISTRY 1 18 3186 - 3192 2003年 [査読有り][通常論文]
     
    Periodic leaf-movement of legumes is called nyctinasty and has been known since the age of Alexander the Great. We found that nyctinasty is controlled by a periodic change of the internal concentration of leaf-opening and leaf-closing substances in the plant body. Now, we have developed novel fluorescent probes (1) based on the structure of cis-p-coumaroylagmatine (3), which was isolated as a leaf-opening substance of Albizzia juribrissin Durazz. Binding experiments using probe 1 showed that Albizza plants have receptors for a leaf-opening substance in their motor cells. By using probes 1 we then found that genus-specific receptors are involved in nyctinasty.
  • N Takada, E Kato, K Ueda, S Yamamura, M Ueda
    TETRAHEDRON LETTERS 43 43 7655 - 7658 2002年10月 [査読有り][通常論文]
     
    We isolated 4-O-beta-D-glucopyranosyl-trans-p-coumarate (1), the leaf-opening Substance of Sesbania exaltata Cory. The leaf-movement inhibitor, designed on the chemical mechanism of nyctinasty, could keep the leaves of S. exaltata open till the leaves withered and died. (C) 2002 Elsevier Science Ltd. All rights reserved.

MISC

講演・口頭発表等

  • 糖代謝を調節して血糖値を「下げる」機能性食品の開発  [招待講演]
    加藤英介
    第７回「食と健康」研究会 2014年04月 公開講演，セミナー，チュートリアル，講習，講義等
  • ヒドロキシアミンの骨格筋細胞に対する糖取り込み促進作用とそ の作用機構解析  [通常講演]
    木村 太郎, 加藤 英介, 町川 司, 木村 駿介, 片山 紳司, 川端 潤
    日本農芸化学会2014年度大会 2014年03月 口頭発表（一般）
  • マカ由来のインスリン様活性物質の探索  [通常講演]
    片山 紳司, 町川 司, 加藤 英介, 川端 潤
    日本農芸化学会2014年度大会 2014年03月 口頭発表（一般）
  • レモングラスからのインスリン様活性物質探索  [通常講演]
    町川 司, 加藤 英介, 川端 潤
    日本農芸化学会2014年度大会 2014年03月 口頭発表（一般）
  • 蓮芯に含まれる筋細 胞の糖取り込み促進活性成分の探索  [通常講演]
    加藤 英介, 木村 太郎, 稲垣 洋 介, 藤田 裕之, 川端 潤
    日本農芸化学会2014年度大会 2014年03月 口頭発表（一般）
  • ヒドロキシアミンの糖取り込み促進作用とその作用機構解析  [通常講演]
    木村 太郎, 加藤 英介, 町川 司, 木村 駿介, 片山 紳司, 川端 潤
    平成２５年度公益社団法人日本農芸化学会北海道支部講演会 2013年11月 口頭発表（一般）

担当経験のある科目（授業）

  • 食品機能化学II北海道大学
  • 有機化学２北海道大学
  • 食品科学特論北海道大学
  • 化学実験II北海道大学
  • 化学II北海道大学

所属学協会

  • 日本栄養・食糧学会   日本農芸化学会   日本化学会   日本味と匂学会   日本食品分析学会   

共同研究・競争的資金等の研究課題

  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2023年04月 -2026年03月 
    代表者 : 加藤 英介
  • 健康寿命の延長を目指したコメ糠成分の機能解析
    (公財) エリザベス・アーノルド富士財団：(公財) エリザベス・アーノルド富士財団 令和4年度学術研究助成
    研究期間 : 2022年09月 -2023年08月 
    代表者 : 加藤 英介
  • 苦味受容体を介した食品の健康機能
    一般財団法人糧食研究会：一般財団法人糧食研究会 2022年度一般公募研究
    研究期間 : 2022年08月 -2023年08月 
    代表者 : 加藤 英介
  • 科学技術振興機構：産学が連携した研究開発成果の展開 研究成果展開事業 研究成果最適展開支援プログラム(A-STEP) トライアウト トライアウト
    研究期間 : 2022年 -2023年 
    代表者 : 加藤 英介
     
    ストレスや加齢によりテストステロンが欠乏すると男性も更年期障害を生じ、種々の体調不良の原因となる。本課題では、「食」による男性更年期予防を目指し、男性更年期対策食品原料の開発手法の構築と、実験動物レベルでのテストステロン量増加効果の実証を行い、男性更年期対策食品の開発基盤を構築する。
  • 体内に発現する苦味受容体の機能解析
    公益財団法人 浦上食品・食文化振興財団：令和2年度 (公財)浦上食品・食文化振興財団 学術研究助成
    研究期間 : 2020年10月 -2022年03月 
    代表者 : 加藤 英介
  • 日本学術振興会：科学研究費補助金（基盤研究(C)）
    研究期間 : 2019年04月 -2022年03月 
    代表者 : 加藤英介
  • 公益財団法人エリザベス・アーノルド富士財団：令和元年度学術研究助成
    研究期間 : 2019年04月 -2020年03月 
    代表者 : 加藤英介
  • 苦味成分による脂肪細胞機能調節の解析
    公益財団法人 三島海雲記念財団：平成30年度 学術研究奨励金
    研究期間 : 2018年07月 -2019年06月 
    代表者 : 加藤英介
  • 消化管上皮細胞機能を調節する食品素材と生物活性成分の探索 研究課題
    文部科学省：科学研究費補助金(若手研究(B))
    研究期間 : 2017年04月 -2019年03月 
    代表者 : 加藤英介
  • 文部科学省：科学研究費補助金(若手研究(B))
    研究期間 : 2013年 -2015年 
    代表者 : 加藤 英介
     
    糖尿病は慢性的な高血糖症状を呈する生活習慣病であり、世界的な問題として取り上げられているため、治療法の開発は急務である。ところが糖尿病治療薬は病態維持を主眼としているため糖尿病を完治する医薬品は存在しない。本研究では糖尿病を治療できる可能性のある生物活性物質として筋細胞の糖取り込み促進物質の探索、機能解析を行った。その結果、糖取り込み促進活性物質として報告されているネオヘスペリドースの作用機構を明らかとした。また、新たな活性物質としてヒゲナミン配糖体、ヒドロキシアミン、不飽和脂肪酸、ピペリンなど各種同定した。さらにヒゲナミン配糖体とヒドロキシアミンの作用機構に関しても明らかとした。
  • 高齢者の筋力維持に有用な食素材の探索
    公益財団法人 北海道科学技術総合振興センター：研究シーズ発掘補助金（札幌フードTalent補助金）
    研究期間 : 2013年08月 -2014年03月 
    代表者 : 加藤英介
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2009年 -2011年 
    代表者 : 川端 潤, 加藤 英介
     
    膵α-アミラーゼの阻害は肥満、糖尿病抑制に効果的である。しかし、この酵素はグルコースの連鎖を基質として認識するという特性から、親和性の高い低分子阻害剤がほとんど知られていない。本研究では、α-アミラーゼの基質認識特異性を積極的に利用した分子を阻害剤として設計、合成して新たな低分子α-アミラーゼ阻害剤をつくりだした。さらに、今後の阻害剤設計に有用なα-アミラーゼの基質認識特性についても明らかとした。

産業財産権


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