Researcher Profile and Settings

Affiliation

• Research Faculty of Agriculture　Fundamental AgriScience Research　Bioscience and Chemistry

Job Title

• Associate Professor

Degree

• Ph. D.（2007/03 Tohoku University）

URL

http://kaken.nii.ac.jp/d/r/40466446.ja.html

Research funding number

• 40466446

ORCID ID

•  https://orcid.org/0000-0001-9322-8589

J-Global ID

• 201301093124422719

Research Interests

• Bitter taste receptor   obesity   糖尿病   酵素阻害剤   

Research Areas

• Life sciences / Food sciences
• Life sciences / Bioorganic chemistry

Educational Organization

•  Bachelor's degree program　School of Agriculture
•  Master's degree program　Graduate School of Agriculture
•  Doctoral (PhD) degree program　Graduate School of Agriculture

Academic & Professional Experience

• 2020/07 - Today Hokkaido University Graduate School of Agriculture Research Faculty of Agriculture Associate Professor
• 2016/01 - 2020/06 Hokkaido University Graduate School of Agriculture Research Faculty of Agriculture
• 2007/09 - 2015/12 Hokkaido University Graduate School of Agriculture Research Faculty of Agriculture

Education

• 2004/04 - 2007/03  Tohoku University  Graduate School of Science  Department of Chemistry
• 2002/04 - 2004/03  Keio University  Graduate School of Science and Technology
• 1998/04 - 2002/03  Keio University  Faculty of Science and Technology  Department of Chemistry

Association Memberships

• JAPAN SOCIETY FOR BIOSCIENCE, BIOTECHNOLOGY, AND AGROCHEMISTRY   THE CHEMICAL SOCIETY OF JAPAN   

Research Activities

Published Papers

• Bioactive Components in Black Currant Fruit, Red Perilla (Shiso) Leaf, and Chinese Sweet Tea That Enhance Testosterone Production in Leydig Cells and Their Combined Effect in Male Mice

  Eisuke Kato, Yosuke Inagaki, Hiromi Kayooka, Yusuke Adachi, Tomoaki Nagase, Naofumi Terada, Ai Tsuruma

  ACS Food Science & Technology 2024/05/17
• Flavan-3-ols, flavonoids, anthocyanidins and triterpenoids induces TIE2 phosphorylation -a candidate target for the vascular protective effects

  Saki Igarashi, Sayaka Hioki, Naoto Sakamaru, Asahi Suzuki, Mihoko Kurokawa, Eisuke Kato

  Natural Product Research 2024/04/12
• α-Tocotrienol in rice bran enhances steroidogenesis in mouse Leydig cell via increased gene expression of steroidogenic acute regulatory protein and induction of its mitochondrial translocation

  Naofumi Terada, Tomoaki Nagase, Hiromi Kayooka, Yusuke Adachi, Eisuke Kato

  Bioscience, Biotechnology, and Biochemistry 88 (2) 189 - 195 2024/01/24 [Refereed][Not invited]
  
• Association of Bitter Taste Receptors with Obesity and Diabetes and Their Role in Related Tissues

  Eisuke Kato, Shota Oshima

  Receptors 2023/12/05 [Refereed]
  
• Murine fecal microRNAs alter the composition of cultured gut microbiota

  Fumina Ohsaka, Mayuko Yamaguchi, Yuka Teshigahara, Moeka Yasui, Eisuke Kato, Kei Sonoyama

  Biochemical and Biophysical Research Communications 685 149184 - 149184 0006-291X 2023/12
• Taste 2 Receptor Is Involved in Differentiation of 3T3-L1 Preadipocytes

  Shunsuke Kimura, Ai Tsuruma, Eisuke Kato

  International Journal of Molecular Sciences 23 (15) 8120 - 8120 2022/07/23 [Refereed][Not invited]
   

  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.
• Saponins are responsible for the anti-obesogenic activity of Acacia concinna

  Zhao Zhuoyue, Wijitrapha Ruangaram, Eisuke Kato

  Journal of Natural Medicines 75 (4) 1005 - 1013 1340-3443 2021/09/21 [Refereed][Not invited]
  
• Proteinous pancreatic lipase inhibitor is responsible for the antiobesity effect of young barley (Hordeum vulgare L.) leaf extract

  Eisuke Kato, Ai Tsuruma, Ayaka Amishima, Hiroshi Satoh

  Bioscience, Biotechnology, and Biochemistry 85 (8) 1885 - 1889 2021/07/23 [Refereed][Not invited]
   

  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.
• Post-harvest and Extraction Conditions for the Optimum Alpha Glucosidase Inhibitory Activity of Stenochlaena palustris

  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 2086-9614 2021/07/19 [Refereed][Not invited]
  
• TAS2R expression profile in brown adipose, white adipose, skeletal muscle, small intestine, liver and common cell lines derived from mice

  Eisuke Kato

  Gene Reports 20 100763 - 100763 2452-0144 2020/09 [Refereed][Not invited]
  
• Selection of Thai Medicinal Plants with Anti-Obesogenic Potential via In Vitro Methods

  Wijitrapha Ruangaram, Eisuke Kato

  Pharmaceuticals 13 (4) 56 - 56 2020/03/29 [Refereed][Not invited]
   

  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.
• Silychristin derivatives conjugated with coniferylalcohols from silymarin and their pancreatic α-amylase inhibitory activity

  Eisuke Kato, Natsuka Kushibiki, Hiroshi Satoh, Jun Kawabata

  Natural Product Research 34 (6) 759 - 765 1478-6419 2020/03/18 [Refereed][Not invited]
  
• Quassinoids in Brucea javanica are potent stimulators of lipolysis in adipocytes

  Lucy Lahrita, Kenta Moriai, Ryohei Iwata, Kazuki Itoh, Eisuke Kato

  Fitoterapia 137 104250 - 104250 0367-326X 2019/09 [Refereed][Not invited]
  
• Bioactive compounds in plant materials for the prevention of diabetesand obesity

  Eisuke Kato

  Bioscience, Biotechnology, and Biochemistry 83 (6) 975 - 985 0916-8451 2019/06/03 [Refereed][Invited]
   

  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.
• Macrocarpal C isolated from Eucalyptus globulus inhibits dipeptidyl peptidase 4 in an aggregated form

  Eisuke Kato, Kazuhiro Kawakami, Jun Kawabata

  Journal of Enzyme Inhibition and Medicinal Chemistry 33 (1) 106 - 109 1475-6366 2018/01/01 [Refereed][Not invited]
  
• Ability of higenamine and related compounds to enhance glucose uptake in L6 cells

  Eisuke Kato, Shunsuke Kimura, Jun Kawabata

  BIOORGANIC & MEDICINAL CHEMISTRY 25 (24) 6412 - 6416 0968-0896 2017/12 [Refereed][Not invited]
   

  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.
• Synthesis and Detailed Examination of Spectral Properties of (S)- and (R)-Higenamine 4 '-O-beta-D-Glucoside and HPLC Analytical Conditions to Distinguish the Diastereomers

  Eisuke Kato, Ryohei Iwata, Jun Kawabata

  MOLECULES 22 (9) 1450  1420-3049 2017/09 [Refereed][Not invited]
   

  Higenamine is a tetrahydroisoquinoline present in several plants that has beta-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-beta-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-beta-D-glucoside was determined to be a mixture of isomers.
• Isolation and lipolytic activity of eurycomanone and its epoxy derivative from Eurycoma longifolia

  Lucy Lahrita, Ryota Hirosawa, Eisuke Kato, Jun Kawabata

  BIOORGANIC & MEDICINAL CHEMISTRY 25 (17) 4829 - 4834 0968-0896 2017/09 [Refereed][Not invited]
   

  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.
• Intestinal alpha-Glucosidase Inhibitors in Achillea millefolium

  Kota Noda, Eisuke Kato, Jun Kawabata

  NATURAL PRODUCT COMMUNICATIONS 12 (8) 1259 - 1261 1934-578X 2017/08 [Refereed][Not invited]
   

  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.
• Astilbe thunbergii reduces postprandial hyperglycemia in a type 2 diabetes rat model via pancreatic alpha-amylase inhibition by highly condensed procyanidins

  Eisuke Kato, Natsuka Kushibiki, Yosuke Inagaki, Mihoko Kurokawa, Jun Kawabata

  BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 81 (9) 1699 - 1705 0916-8451 2017 [Refereed][Not invited]
   

  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.
• Synthesis and study of the pancreatic alpha-amylase inhibitory activity of methyl acarviosin and its derivatives

  Eisuke Kato, Fumiaki Chikahisa, Jun Kawabata

  TETRAHEDRON LETTERS Elsevier {BV} 57 (12) 1365 - 1367 0040-4039 2016/03 [Refereed][Not invited]
   

  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.
• Isolation of rugosin A, B and related compounds as dipeptidyl peptidase-IV inhibitors from rose bud extract powder

  Eisuke Kato, Yuta Uenishi, Yosuke Inagaki, Mihoko Kurokawa, Jun Kawabata

  BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 80 (11) 2087 - 2092 0916-8451 2016 [Refereed][Not invited]
   

  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.
• Higenamine 4 '-O-beta-D-glucoside in the lotus plumule induces glucose uptake of L6 cells through beta 2-adrenergic receptor

  Eisuke Kato, Yosuke Inagaki, Jun Kawabata

  BIOORGANIC & MEDICINAL CHEMISTRY Elsevier {BV} 23 (13) 3317 - 3321 0968-0896 2015/07 [Refereed][Not invited]
   

  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.
• Uncovering potential of Indonesian medicinal plants on glucose uptake enhancement and lipid suppression in 3T3-L1 adipocytes

  Lucy Lahrita, Eisuke Kato, Jun Kawabata

  JOURNAL OF ETHNOPHARMACOLOGY 168 229 - 236 0378-8741 2015/06 [Refereed][Not invited]
   

  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.
• Selective purification of intestinal maltase complex by affinity chromatography employing an uncompetitive inhibitor as the ligand

  Eisuke Kato, Hiroki Tsuji, Jun Kawabata

  TETRAHEDRON 71 (9) 1419 - 1424 0040-4020 2015/03 [Refereed][Not invited]
   

  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.
• alpha-Amylase Inhibitory Triterpene from Abrus precatorius Leaves

  Ryuta Yonemoto, Miyuki Shimada, Maria D. P. T. Gunawan-Puteri, Eisuke Kato, Jun Kawabata

  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 62 (33) 8411 - 8414 0021-8561 2014/08 [Refereed][Not invited]
   

  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.
• Hydroxylamine enhances glucose uptake in C2C12 skeletal muscle cells through the activation of insulin receptor substrate 1

  Taro Kimura, Eisuke Kato, Tsukasa Machikawa, Shunsuke Kimura, Shinji Katayama, Jun Kawabata

  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 445 (1) 6 - 9 0006-291X 2014/02 [Refereed][Not invited]
   

  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.
• Identification of alpha-glucosidase inhibitors from the leaves of Pluchea indica (L.) Less., a traditional Indonesian herb: promotion of natural product use

  Ines Septi Arsiningtyas, Maria D. P. T. Gunawan-Puteri, Eisuke Kato, Jun Kawabata

  NATURAL PRODUCT RESEARCH 28 (17) 1350 - 1353 1478-6419 2014 [Refereed][Not invited]
   

  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.
• Identification of hydroxychavicol and its dimers, the lipase inhibitors contained in the Indonesian spice, Eugenia polyantha

  Eisuke Kato, Ryo Nakagomi, Maria D. P. T. Gunawan-Puteri, Jun Kawabata

  FOOD CHEMISTRY 136 (3-4) 1239 - 1242 0308-8146 2013/02 [Refereed][Not invited]
   

  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.
• Substrate-like water soluble lipase inhibitors from Filipendula kamtschatica

  Eisuke Kato, Michitsugu Yama, Ryo Nakagomi, Toshiro Shibata, Keizo Hosokawa, Jun Kawabata

  BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 22 (20) 6410 - 6412 0960-894X 2012/10 [Refereed][Not invited]
   

  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.
• Synthesis and the Intestinal Glucosidase Inhibitory Activity of 2-Aminoresorcinol Derivatives toward an Investigation of Its Binding Site

  Eisuke Kato, Kenichi Oikawa, Keisuke Takahashi, Jun Kawabata

  BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 76 (5) 1044 - 1046 0916-8451 2012/05 [Refereed][Not invited]
   

  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.
• Screening and Identification of Disaccharides with Insulin Mimetic Activity against L6 Cells

  Kazuaki Yamasaki, Ryogo Hishiki, Eisuke Kato, Jun Kawabata

  BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 76 (4) 841 - 842 0916-8451 2012/04 [Refereed][Not invited]
   

  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.
• alpha-Amylase inhibitors from an Indonesian medicinal herb, Phyllanthus urinaria

  Maria D. P. T. Gunawan-Puteri, Eisuke Kato, Jun Kawabata

  JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 92 (3) 606 - 609 0022-5142 2012/02 [Refereed][Not invited]
   

  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
• Synthesis and alpha-amylase inhibitory activity of glucose-deoxynojirimycin conjugates

  Eisuke Kato, Naoya Iwano, Akihiko Yamada, Jun Kawabata

  TETRAHEDRON 67 (40) 7692 - 7702 0040-4020 2011/10 [Refereed][Not invited]
   

  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.
• Study of Kaempferol Glycoside as an Insulin Mimic Reveals Glycon To Be the Key Active Structure

  Kazuaki Yamasaki, Ryogo Hishiki, Eisuke Kato, Jun Kawabata

  ACS MEDICINAL CHEMISTRY LETTERS 2 (1) 17 - 21 1948-5875 2011/01 [Refereed][Not invited]
   

  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.
• Study on Insulin-Mimetic Activity of Kaempferol 3-Ο-neohesperidoside

  Yamasaki Kazuaki, Hishiki Ryogo, Kato Eisuke, Kawabata Jun

  Symposium on the Chemistry of Natural Products, symposium papers 天然有機化合物討論会 (52) 409 - 414 2010/09/01 

  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.
• Search for alpha-glucosidase and alpha-amylase inhibitors from Indonesian medicinal plants

  M. Gunawan-Puteri, E. Kato, J. Kawabata

  PLANTA MEDICA 76 (12) 1182 - 1182 0032-0943 2010/08 [Refereed][Not invited]
  
• Glucose uptake enhancing activity of puerarin and the role of C-glucoside suggested from activity of related compounds

  Eisuke Kato, Jun Kawabata

  BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 20 (15) 4333 - 4336 0960-894X 2010/08 [Refereed][Not invited]
   

  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.
• Methyl Caffeate as an alpha-Glucosidase Inhibitor from Solanum torvum Fruits and the Activity of Related Compounds

  Keisuke Takahashi, Yasuyuki Yoshioka, Eisuke Kato, Shigeki Katsuki, Osamu Iida, Keizo Hosokawa, Jun Kawabata

  BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 74 (4) 741 - 745 0916-8451 2010/04 [Refereed][Not invited]
   

  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.
• Affinity purification and characterization of a key enzyme responsible for circadian rhythmic control of nyctinasty in Lespedeza cuneata L.

  Eisuke Kato, Takehiko Sasaki, Minoru Ueda

  BIOORGANIC & MEDICINAL CHEMISTRY 16 (8) 4600 - 4616 0968-0896 2008/04 [Refereed][Not invited]
   

  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.
• Affinity purification of the key enzyme of nyctinasty controlling the rhythm of leaf movement using gluconamidine ligand

  Eisuke Kato, Takehiko Sasaki, Tadahiro Kumagai, Minoru Ueda

  TETRAHEDRON LETTERS 48 (13) 2409 - 2413 0040-4039 2007/03 [Refereed][Not invited]
   

  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.
• Synthesis of novel ginkgolide photoaffinity-biotin probes

  Eisuke Kato, Rachel Howitt, Sergei V. Dzyuba, Koji Nakanishi

  ORGANIC & BIOMOLECULAR CHEMISTRY 5 (23) 3758 - 3761 1477-0520 2007 [Refereed][Not invited]
   

  Site-selective introduction of biotin and benzophenone probes onto ginkgolide scaffolds is described.
• Bioorganic chemistry of nyctinasty using functional probes

  M Ueda, T Fujii, E Kato, T Sugimoto, N Kato

  JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN 64 (2) 117 - 129 0037-9980 2006/02 [Refereed][Not invited]
   

  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.
• Bioorganic studies on plant movement, from natural products to its receptor

  Mitsuru Shoji, Eisuke Kato, Yoko Nakamura, Tomohiko Fujii, Yoshiyuki Manabe, Minoru Ueda

  CHEMICAL RECORD 6 (6) 344 - 355 1527-8999 2006 [Refereed][Not invited]
   

  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.
• Concise synthesis of glyconoamidines as affinity ligands for the purification of beta-glucosidase involved in control of some biological events including plant leaf movement

  E Kato, T Kumagai, M Ueda

  TETRAHEDRON LETTERS 46 (29) 4865 - 4869 0040-4039 2005/07 [Refereed][Not invited]
   

  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.
• Synthetic inhibitor of leaf-closure that reveals the biological importance of leaf-movement for the survival of leguminous plants

  E Kato, H Nagano, S Yamamura, M Ueda

  TETRAHEDRON 59 (31) 5909 - 5917 0040-4020 2003/07 [Refereed][Not invited]
   

  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.
• Fluorescence studies on nyctinasty using fluorescence labeled cis-p-coumaroylagmatine, a leaf-opening substance of Albizzia plants: existence of genus-specific receptor for leaf-movement factor

  H Nagano, E Kato, S Yamamura, M Ueda

  TETRAHEDRON LETTERS 44 (14) 2953 - 2956 0040-4039 2003/03 [Refereed][Not invited]
   

  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.
• Synthetic Inhibitor of Leaf-closure Designed on the Chemical Mechanism of Leaf-movement

  E. Kato, H. Nagano, S. Yamamura, M.Ueda

  Tetrahedron 59 (31) 5909 - 5917 0040-4020 2003 [Refereed][Not invited]
  
• Fluorescence studies on nyctinasty which suggest the existence of genus-specific receptors for leaf-movement factor

  H Nagano, E Kato, S Yamamura, M Ueda

  ORGANIC & BIOMOLECULAR CHEMISTRY 1 (18) 3186 - 3192 1477-0520 2003 [Refereed][Not invited]
   

  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.
• A novel leaf-movement inhibitor of a nyctinastic weed, Sesbania exaltata Cory, designed on a naturally occurring leaf-opening substance and its application to a potential, highly selective herbicide

  N Takada, E Kato, K Ueda, S Yamamura, M Ueda

  TETRAHEDRON LETTERS 43 (43) 7655 - 7658 0040-4039 2002/10 [Refereed][Not invited]
   

  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.

Conference Activities & Talks

• 糖代謝を調節して血糖値を「下げる」機能性食品の開発  [Invited]

  加藤英介

  第７回「食と健康」研究会  2014/04
• 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  [Not invited]

  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  2014/03
• マカ由来のインスリン様活性物質の探索  [Not invited]

  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  2014/03
• レモングラスからのインスリン様活性物質探索  [Not invited]

  町川 司, 加藤 英介, 川端 潤

  日本農芸化学会2014年度大会  2014/03
• 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  [Not invited]

  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  2014/03
• 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  [Not invited]

  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  2013/11

MISC

• α‐グルコシダーゼの阻害部位同定に向けた2‐アミノレゾルシノールのプローブ化研究

  及川健一, 加藤英介, 川端潤  日本農芸化学会大会講演要旨集  2011-  177  2011/03/05  [Not refereed][Not invited]
  
• 基質認識機構を利用したα‐アミラーゼ阻害剤の合成と活性

  加藤英介, 山田有二, 山田暁彦, 安藤まり子, 川端潤  日本農芸化学会大会講演要旨集  2011-  19  2011/03/05  [Not refereed][Not invited]
  
• オニシモツケ地上部中の新規膵リパーゼ阻害成分の単離

  山理嗣, 柴田敏郎, 細川敬三, 加藤英介, 川端潤  日本農芸化学会大会講演要旨集  2011-  69  2011/03/05  [Not refereed][Not invited]
  
• インドネシア産植物由来α‐アミラーゼ阻害成分の探索

  島田実幸, GUNAWAN‐PUTERI Maria, 加藤英介, 川端潤  日本農芸化学会大会講演要旨集  2011-  68  2011/03/05  [Not refereed][Not invited]
  
• Candida albicansの菌糸形成に影響する消化管腔内因子

  園山慶, 中田麻友美, 加藤英介  日本農芸化学会大会講演要旨集  2011-  269  2011/03/05  [Not refereed][Not invited]
  
• フェノールカルボン酸類のラジカル消去機構(31)―水系での新規プロトカテキュ酸メチル二量体の生成―

  上杉信太郎, 加藤英介, 川端潤  日本農芸化学会東北支部大会プログラム・講演要旨集  145th-  55  2010/09/27  [Not refereed][Not invited]
  
• グルコース‐デオキシノジリマイシン複合体の合成とα‐アミラーゼ阻害活性

  加藤英介, 山田有二, 山田暁彦, 安藤まり子, 川端潤  日本農芸化学会東北支部大会プログラム・講演要旨集  145th-  55  2010/09/27  [Not refereed][Not invited]
  
• Kaempferol3‐O‐neohesperidosideのインスリン様活性に関する研究

  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  52nd-  409  -414  2010/09/01  [Not refereed][Not invited]
  
• フェノールカルボン酸類のラジカル消去機構(30)―水系での新規プロトカテキュ酸二量体の生成―

  上杉信太郎, 加藤英介, 川端潤  日本農芸化学会大会講演要旨集  2010-  273  2010/03/05  [Not refereed][Not invited]
  
• Kaempferol配糖体および関連化合物の合成とそのインスリン様活性

  山崎一諒, 加藤英介, 川端潤  日本農芸化学会大会講演要旨集  2010-  46  2010/03/05  [Not refereed][Not invited]
  
• イソフラボン配糖体puerarinの糖取込促進活性に関する構造活性相関研究

  加藤英介, 川端潤  日本農芸化学会大会講演要旨集  2010-  46  2010/03/05  [Not refereed][Not invited]
  
• 2‐アミノレゾルシノール誘導体の合成とα‐グルコシダーゼ阻害活性評価

  及川健一, 高橋敬典, 加藤英介, 加藤英介, 川端潤, 川端潤  日本農芸化学会大会講演要旨集  2010-  174  2010/03/05  [Not refereed][Not invited]
  
• マウス盲腸内容物中に含まれるCandida albicans菌糸形成促進物質の探索

  中田麻友美, 武村直紀, 秦枝里奈, 上杉信太郎, 加藤英介, 園山慶  日本栄養・食糧学会大会講演要旨集  63rd-  222  2009/05/01  [Not refereed][Not invited]
  
• 光反応基を導入したバイカレイン誘導体の合成と応用

  高橋敬典, 加藤英介, 川端潤  日本農芸化学会大会講演要旨集  2009-  201  2009/03/05  [Not refereed][Not invited]
  
• Kaempferol配糖体のインスリン様作用と構造活性相関研究

  山崎一諒, 加藤英介, 川端潤  日本農芸化学会大会講演要旨集  2009-  222  2009/03/05  [Not refereed][Not invited]
  
• イソフラボン配糖体puerarinのインスリン様作用に関する研究

  加藤英介, 川端潤  日本農芸化学会大会講演要旨集  2009-  221  2009/03/05  [Not refereed][Not invited]
  
• 米国コロンビア大学でのポスドク生活 : 中西研究室でのギンコライドに関する研究

  加藤 英介  化学と生物  47-  (2)  143  -147  2009/02/01  [Not refereed][Not invited]
   

  「海外だより」を執筆している現在から1年と2ヵ月前までアメリカ，ニューヨーク州コロンビア大学に留学していました．すでに日本に帰っている筆者が「海外だより」を書くのは少々違和感がありますが，留学中の経験など紹介させていただきます．筆者は特別深い理由があって留学を決めたのではなく，博士2年当時に企業への就職の意志があまりなかったため，ポスドク先として適当なところはないかと考えていました．特に国内・国外はあまり気にせず見繕っていましたが，結局は当時の教授の薦めもあって，コロンビア大学の中西香爾教授の研究室に決めました．
• サブサイト認識を志向したα‐アミラーゼ阻害剤の設計と合成

  岩野直哉, 加藤英介, 川端潤  日本農芸化学会大会講演要旨集  2008-  127  2008/03/05  [Not refereed][Not invited]
  
• バイカレインのビニローグ誘導体のスクラーゼ阻害活性

  高橋敬典, 加藤英介, 川端潤  日本農芸化学会大会講演要旨集  2008-  126  2008/03/05  [Not refereed][Not invited]
  
• Huisgen環化反応を利用したコレステロール吸収阻害活性検定法の確立

  鳥巣哲生, 加藤英介, 川端潤  日本農芸化学会北海道支部・日本土壌肥料学会北海道支部・日本生物工学会北日本支部・日本応用糖質科学会北海道支部・北海道農芸化学協会合同学術講演会講演要旨  2008-  24  2008  [Not refereed][Not invited]
  
• 就眠運動のリズムを調節する鍵酵素の精製とその性質

  加藤英介, 佐々木健彦, 上田実  日本化学会講演予稿集  87th-  (2)  1244  2007/03/12  [Not refereed][Not invited]
  
• Affinity Purification of the Key Enzyme .BETA.-Glucosidase Controlling Nyctinastic Rhythm Movement

  KATO EISUKE, KUMAGAI TADAHIRO, UEDA MINORU  日本化学会講演予稿集  86th-  (2)  1318  2006/03/13  [Not refereed][Not invited]
  
• Synthesis of Glyconoamidines as a Potent Inhibitor of .BETA.-Glucosidase Using Non-protected Thionolactum.

  KUMAGAI TADAHIRO, KATO EISUKE, UEDA MINORU  日本化学会講演予稿集  86th-  (2)  1319  2006/03/13  [Not refereed][Not invited]
  
• Bioorganic chemistry of nyctinasty using functional probes

  M Ueda, T Fujii, E Kato, T Sugimoto, N Kato  JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN  64-  (2)  117  -129  2006/02  [Not refereed][Not invited]
   

  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.
• Bioorganic chemistry of nyctinasty using functional probes

  M Ueda, T Fujii, E Kato, T Sugimoto, N Kato  JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN  64-  (2)  117  -129  2006/02  [Not refereed][Not invited]
   

  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.
• グルコノアミジン型阻害剤による就眠運動の鍵酵素β‐グルコシダーゼのアフィニティー精製

  加藤英介, 熊谷忠浩, 上田実  天然有機化合物討論会講演要旨集  47th-  (47)  229  -234  2005/09/15  [Not refereed][Not invited]
   

  Nyctinastic movement of leguminous plants is controlled by the glucosylated leaf-movement factor, whose concentration changes throughout the day, regulated by β-glucosidase. Therefore, in order to understand the controlling mechanism of the movement by circadian clock, purification of this key enzymeis essential. Many isozymes of β-glucosidase are known to exist in plant body. To purify the key enzyme from this mixture, affinity chromatography is a powerful tool. We have tried two affinity gel 4 and 5, which is an usual tool used for purification of β-glucosidase. But they were both not effective, from the luck of aglycon part or the low inhibition constant. According to this experiment, we concluded that affinity ligand should be an analog of the leaf-movement factor, and at the same time it should be a strong inhibitor. Gluconoamidine is known to show strong inhibition toward β-glucosidase. Thus, we have planed to synthesize 7, an analog of leaf-movement factor with gluconoamidine part, instead of glucose as the glucoside part. Several methods are known for the synthesis of gluconoamidine compound using thionolactam(6) and amine compound. But there are several restriction. 1) Benzyl protected sugar derivative are necessary 2) Needs of a reactive amine group. And also, in some cases the epimerization at C2 of the sugar moiety occurs. To overcome these restrictions, we have developed a novel method for the synthesis of gluconoamidine compound. And by employing this method we have synthesized 7. Compound 7 showed strong and selective inhibition toward commercially available β-glucosidase. Encouraged by this result we synthesized an affinity gel 16, using 7 as a ligand. Purification of the crude enzyme, extracted from Lespedeza cuneata, by affinity gel 16 was effective. We are now working on further purification of the key enzyme.
• 植物就眠運動の鍵酵素精製を目指したグルコノアミジン型アフィニティーゲルの開発

  加藤英介, 熊谷忠浩, 上田実  化学系学協会東北大会プログラムおよび講演予稿集  2005-  186  2005/09/15  [Not refereed][Not invited]
  
• 44 Affinity Purification of the Key Enzyme β-Glucosidase Controlling Nyctinastic Movement of Leguminous Plant by Gluconoamidine Type Inhibitor

  Kato Eisuke, Kumagai Tadahiro, Ueda Minoru  Symposium on the Chemistry of Natural Products, symposium papers  0-  (47)  229  -234  2005/09/15  [Not refereed][Not invited]
   

  Nyctinastic movement of leguminous plants is controlled by the glucosylated leaf-movement factor, whose concentration changes throughout the day, regulated by β-glucosidase. Therefore, in order to understand the controlling mechanism of the movement by circadian clock, purification of this key enzymeis essential. Many isozymes of β-glucosidase are known to exist in plant body. To purify the key enzyme from this mixture, affinity chromatography is a powerful tool. We have tried two affinity gel 4 and 5, which is an usual tool used for purification of β-glucosidase. But they were both not eff...
• グルコノアミジン類の効率的合成と就眠運動の鍵酵素β‐グルコシダーゼの精製

  加藤英介, 熊谷忠浩, 上田実  万有生命科学振興国際交流財団仙台シンポジウム  16th-  48  2005/05/28  [Not refereed][Not invited]
  
• Purification study of the key enzyme .BETA.-glucosidase controlling nyctinasty using amidine type leaf-opening substance analog

  KATO EISUKE, KUMAGAI TADAHIRO, UEDA MINORU  日本化学会講演予稿集  85th-  (2)  881  2005/03/11  [Not refereed][Not invited]
  
• Purification of .BETA.-glucosidase, the key enzyme of nyctinasty, which controls the nyctinastic movement of leguminous plants

  KATO EISUKE, YAMAMURA SHOSUKE, UEDA MINORU  日本化学会講演予稿集  84th-  (2)  1028  2004/03/11  [Not refereed][Not invited]
  
• Development of Inhibitor of Nyctinasty Based on the Leaf-Opening Substance and Its Application for a Highly Selective Agrochemical

  KATO EISUKE, SUGIMOTO TAKANORI, YAMAMURA SHOSUKE, UEDA MINORU  日本化学会講演予稿集  83rd-  (2)  918  2003/03/03  [Not refereed][Not invited]
  
• The bioorganic Chemical study about nyctinastic leafmovement of Albizzia julibrissin Durazz with fluorescence probe compounds

  NAGANO HIDEHARU, KATO EISUKE, YAMAMURA SHOSUKE, UEDA MINORU  日本化学会講演予稿集  83rd-  (2)  918  2003/03/03  [Not refereed][Not invited]
  
• The Leaf-opening Substance of Sesbania speciosa Taub. and Application for a Highly Selective Agrochemical

  KATO EISUKE, TAKADA AKIRA, UEEDA KATSUHIRO, YAMAMURA SHOSUKE, UEDA MINORU  日本化学会講演予稿集  82nd-  200  2002/09/10  [Not refereed][Not invited]
  
• 植物はなぜ眠るのか? 就眠運動阻害剤を用いたアプローチと環境調和型アグロケミカルへの応用

  加藤英介, 杉本貴謙, 沢井善行, 上江田捷博, 高田晃, 山村庄亮, 上田実  天然有機化合物討論会講演要旨集  44th-  (44)  397  -402  2002/09/01  [Not refereed][Not invited]
   

  Most legumes close their leaves in the evening, and open them at the morning. This movement is called nyctinasty. "Why does the leguminous plant sleep?" is the unsolvable question about the nyctinasty. Darwin and Bunning had a view to this problem, for example Darwin said that it is a movement to guard against the coldness of the night, and Bunning said it is to prevent reset of the biological clock by moonlight. But it couldn't be a theory cause they didn't have much supporting data. On base of the mechanism of nyctinastic movement, we have synthesized an inhibitor (2) of nyctinastic movement from the leaf-opening substance of Cassia mimosoides L., thinking that legumes don't sleep will be a solution for the question. 2 had successfully inhibited nyctinastic movement and made the plant insomnia. Also we have found that insomnia plant withers in a week or two. And gave a key to solve the question "Why does the leguminous plant sleep?" that nyctinastic movement is essential for leguminous plants to survive. Two factors, that nyctinastic movement is essential for leguminous plants to survive, and leaf-opening substance is specific to each genus, suggested the use of nyctinastic movement inhibitor as the highly specific agrochemical. We have targeted Sesbania exaltata Cory, the weed becoming a problem on soybean plantation in USA. From the extraction of the Sesbania speciosa Taub., predicted to have the same leaf-opening substance with the S. exaltata Cory, we have isolated potassium 4-O-β-D-glucopyranosyl-trans-p-coumarate (11) as the leaf-opening factor. 11 was confirmed to be specific to the Sesbania genus, so next we synthesized an inhibitor (12 and 13) from 11. The synthesized 12 and 13 was first confirmed to be specific to Sesbania genus, and then used to S. exaltata Cory. 12 and 13 had successfully withered the plant and showed the possibility for the use of nyctinastic movement inhibitor as the highly specific agrochemical.
• 68(P-47) Why does the leguminous plant sleep? : Chemical approach using synthetic inhibitor of nyctinasty

  Kato Eisuke, Sugimoto Takanori, Sawai Yoshiyuki, Ueda Katsuhiro, Takada Noboru, Yamamura Shosuke, Ueda Minoru  Symposium on the Chemistry of Natural Products, symposium papers  0-  (44)  397  -402  2002/09/01  [Not refereed][Not invited]
   

  Most legumes close their leaves in the evening, and open them at the morning. This movement is called nyctinasty. "Why does the leguminous plant sleep?" is the unsolvable question about the nyctinasty. Darwin and Bunning had a view to this problem, for example Darwin said that it is a movement to guard against the coldness of the night, and Bunning said it is to prevent reset of the biological clock by moonlight. But it couldn't be a theory cause they didn't have much supporting data. On base of the mechanism of nyctinastic movement, we have synthesized an inhibitor (2) of nyctinastic movem...
• Chemical Study on the Leaf-opening Substance of Sesbania speciosa Taub.

  KATO EISUKE, TAKADA NOBORU, UEDA KATSUHIRO, YAMAMURA SHOSUKE, UEDA MINORU  日本化学会講演予稿集  81st-  (2)  737  2002/03/11  [Not refereed][Not invited]
  

Industrial Property Rights

• 特許6272604:糖取り込み促進剤    2018/01/12

  加藤英介

Awards & Honors

• 2018/03 Japan Society for Bioscience, Biotechnology, and Agrochemistry The Japan Bioscience, Biotechnology and Agrochemistry Society Award for the Encouragement of Young Scientists
   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: KATO, Eisuke

Research Grants & Projects

• Functional analysis of bitter taste receptors in adipocytes and hepatocytes

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2023/04 -2026/03 

  Author : 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

  Date (from‐to) : 2022/09 -2023/08 

  Author : 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

  Date (from‐to) : 2022/08 -2023/08 

  Author : 加藤 英介
• 男性更年期対策食品原料の開発手法の構築

  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

  Date (from‐to) : 2022 -2023 

  Author : 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

  Date (from‐to) : 2020/10 -2022/03 

  Author : 加藤 英介
• 食品成分が標的とする体内の苦味受容体の役割を探る

  日本学術振興会：科学研究費補助金（基盤研究(C)）

  Date (from‐to) : 2019/04 -2022/03 

  Author : 加藤英介
• 米糠成分のステロイドホルモン生合成促進作用

  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

  Date (from‐to) : 2019/04 -2020/03 

  Author : 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

  Date (from‐to) : 2018/07 -2019/06 

  Author : 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))

  Date (from‐to) : 2017/04 -2019/03 

  Author : 加藤英介
• Study on glucose uptake enhancement activity of plant derived compounds with unique and high polar structure

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2013 -2015 

  Author : KATO Eisuke

   

  Diabetes mellitus is a disease that shows high blood glucose level. The disease is currently considered a worldwide problem and development of a method for treatment is highly required task. However, current medicines are developed on a intense to control blood glucose and prevent complications and thus, they are not suitable for completely curing the disease. In this study, bioactive compound that enhance the glucose uptake of muscle cells are studied as a candidate for diabetes mellitus curing compound. The function of the glucose uptake enhancer neohesperidose was revealed and several new glucose uptake enhancers including higenamine glucoside, hydroxylamine, unsaturated fatty acids, piperine were discovered. Also, the function of higenamine glucoside, hydroxylamine are revealed from inhibitor co-incubation experiment.
• 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）

  Date (from‐to) : 2013/08 -2014/03 

  Author : 加藤英介
• Molecular design of amylase inhibitor based on the substrate recognition property of the enzyme

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2009 -2011 

  Author : KAWABATA Jun, KATO Eisuke

   

  Inhibition of the pancreaticα-amylase is useful for the treatment of obesity and diabetes mellitus. However, not many small molecule inhibitors are known for this enzyme due to its characteristic substrate recognition which recognizes chained glucoses. We used this characteristic mode of substrate recognition to design new small moleculeα-amylase inhibitors and synthesized them. These synthetic inhibitors revealed a useful property of the pancreaticα-amylase for further development of the inhibitor.

Educational Activities

Teaching Experience