Idenitification of the endogenous ligand for the sweet taste receptor expressed in pancreatic beta-cells

• Project/Area Number: 25670431
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Gunma University
• Principal Investigator: KOJIMA Itaru 群馬大学, 生体調節研究所, 教授 (60143492)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 甘味受容体 / 膵β細胞 / インスリン分泌 / グルコース / β細胞 / 脂肪細胞 / グルコース感知受容体 / 糖代謝

Outline of Final Research Achievements

The purpose of this study was to identify an endogenous ligand for the sweet taste receptor expressed in pancreatic beta-cells and adipocytes. We initially searched for intracellular compounds which activate the receptor. During the course of the study, we found that glucose is an endogenous ligand for this receptor. We therefore designated this receptor "the glucose-sensing receptor". We investigated the function and physiological role of this receptor in the action of glucose in beta-cells. We found that glucose activates the receptor, facilitates the metabolism in mitochondria and enhances the production of ATP. Since blockade of the receptor results in reduction of insulin secretion, we conclude that glucose-sensing receptor is involved in the action of glucose on insulin secretion. We also studied the changes in the expression of the glucose-sensing receptor in pancreatic beta-cells. The expression of the receptor is markedly reduced after the meal and hyperglycemia.

Research Products

• [Journal Article] Return of the glucoreceptor: Glucose activates the glucose-sensing receptor T1R3 and facilitates metabolism in pancreatic β-cellls. (2015)
  • Author(s): Kojima, I., Nakagawa, Y., Ohtsu, Y., Hamano, K., Medina, J., and Nagasawa, M
  • Journal Title: J Diab Invest Volume: 6 Issue: 3 Pages: 256-263
  • DOI: 10.1111/jdi.12304
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sweet taste-sensing receptor expressed in pancreatic ・-cells : Sweet molecules act as biased agonists (2014)
  • Author(s): Kojima I, Nakagawa Y, Ohtsu Y, Madina A, Nagasawa M
  • Journal Title: Endocr Metab Volume: 29 Issue: 1 Pages: 12-19
  • DOI: 10.3803/enm.2014.29.1.12
  • Peer Reviewed / Open Access
• [Journal Article] Expression of the glucose-sensing receptor T1R3 in pancreatic islet: changes in the expression levels in various nutritional and metabolic states (2014)
  • Author(s): Medina, A., Nakagawa,Y., Ma, J.H., Li L,F., Hamano, K., Akimoto, T., Ninomiya,Y., Kojima,I
  • Journal Title: Endocrine Journal Volume: 61 Issue: 8 Pages: 797-805
  • DOI: 10.1507/endocrj.EJ14-0221
  • NAID: 130004443983
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Diverse signaling systems activated by the sweet taste-sensing recptor in human GLP-1-secreting cells (2014)
  • Author(s): Otsu,Y., Nakagawa,Y., Nagasawa,M., Takeda,S., Arakawa,H. and Kojima,I
  • Journal Title: Mol. Cell. Endocrinol Volume: 394 Issue: 1-2 Pages: 70-79
  • DOI: 10.1016/j.mce.2014.07.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor T1R3 (2014)
  • Author(s): Nakagawa Y, Ohtsu Y, Nagasawa M, Shibata H, Kojima I
  • Journal Title: Endocrine Journal Volume: 61 Issue: 2 Pages: 119-131
  • DOI: 10.1507/endocrj.EJ13-0431
  • NAID: 130004718269
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 Cells. (2013)
  • Author(s): Masubuchi Y., Nakagawa Y., Ma J., Sasaki T., Kitamura T., Yamamoto Y., Kurose H., Kojima I and Shibata H.
  • Journal Title: PLOS ONE Volume: 8
  • Peer Reviewed
• [Journal Article] Involvement of the parasympathetic nervous system in the initiation of regeneration of pancreatic beta-cells (2013)
  • Author(s): Medina, A., Yamada,S., Hara,A., Hamamoto,K. and Kojima,I.
  • Journal Title: Endocr J Volume: 60 Pages: 687-696
  • Peer Reviewed
• [Journal Article] Multimodal function of the sweet taste receptor expressed in pancreatic b-cells: generation of diverse patterns of intracellular signals by sweet agonists. (2013)
  • Author(s): Nakagawa,Y., Nagasawa,M., Mogami,H., Lohse,M., Ninomiya,Y., and Kojima, I.
  • Journal Title: Endocr J Volume: 60 Pages: 1191-1206
  • Peer Reviewed
• [Presentation] グルコース感知受容体T1R3による糖代謝の促進機構 (2014)
  • Author(s): 大津義晃、中川祐子、濱野邦久、李龍飛、荒川浩一、小島至
  • Organizer: 第５７回日本糖尿病学会
  • Place of Presentation: 大阪府大阪市大阪国際会議場
  • Year and Date: 2014-05-24
• [Presentation] 膵β細胞におけるグルコース感知受容体T1R3の発現変化 (2014)
  • Author(s): 中川祐子、Anya Medina、濱野邦久、大津義晃、李龍飛、馬金輝、小島至
  • Organizer: 第５７回日本糖尿病学会
  • Place of Presentation: 大阪府大阪市大阪国際会議場
  • Year and Date: 2014-05-24
• [Presentation] グルコース感知受容体T1R3によるインスリン分泌の制御 (2014)
  • Author(s): 小島至、中川祐子
  • Organizer: 第８７回日本内分泌学会総会
  • Place of Presentation: 福岡市福岡国際会議場
  • Invited
• [Presentation] グルコース作用における甘味受容体の関与 (2013)
  • Author(s): 中川祐子、長澤雅裕、最上秀夫、小島至
  • Organizer: 第５６回に本糖尿病学会年次学術集会
  • Place of Presentation: 熊本市熊本市民会館
• [Presentation] GLP1産生細胞における甘味受容体の「シグナル産生機構 (2013)
  • Author(s): 大津義晃、中川祐子、荒川浩一、小島至
  • Organizer: 第５６回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本市熊本市民会館
• [Presentation] 甘味刺激によるGs活性化は微小間重合とRho活性化を介して脂肪分化を抑制する (2013)
  • Author(s): 増渕洋祐、中川祐子、馬金輝、長澤雅裕、小島至、柴田宏
  • Organizer: 第５６回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本市熊本市民会館