Return of the glucoreceptor: Glucose activates the glucose‐sensing receptor T1R3 and facilitates metabolism in pancreatic β‐cells

Journal of Diabetes Investigation

Itaru Kojima¹  Yuko Nakagawa¹  Yoshiaki Ohtsu¹  Kunihisa Hamano¹  Johan Medina¹ 

[1] Institute for Molecular & Cellular Regulation, Gunma University, Maebashi, Japan

关键词: Glucose;    Insulin secretion;    Sweet taste receptor;   

DOI  :  10.1111/jdi.12304

来源: Wiley

【 摘 要 】

Abstract

Subunits of the sweet taste receptor, namely T1R2 and T1R3, are expressed in mouse pancreatic islets. Quantitatively, the expression of messenger ribonucleic acid for T1R2 is much lower than that of T1R3, and immunoreactive T1R2 is in fact undetectable. Presumably, a homodimer of T1R3 could function as a signaling receptor. Activation of this receptor by adding an artificial sweetener, sucralose, leads to an increase in intracellular adenosine triphosphate ([ATP]_c). This increase in [ATP]_c is observed in the absence of ambient glucose. Sucralose also augments elevation of [ATP]_c induced by methylsuccinate, a substrate for mitochondria. Consequently, activation of T1R3 promotes metabolism in mitochondria and increases [ATP]_c. 3-O-Methylglucose, a non-metabolizable analog of glucose, also increases [ATP]_c. Conversely, knockdown of T1R3 attenuates elevation of [ATP]_c induced by glucose. Hence, glucose promotes its own metabolism by activating T1R3 and augmenting ATP production. Collectively, a homodimer of T1R3 functions as a cell surface glucose-sensing receptor and participates in the action of glucose on insulin secretion. The glucose-sensing receptor T1R3 might be the putative glucoreceptor proposed decades ago by Niki et al. The glucose-sensing receptor is involved in the action of glucose and modulates glucose metabolism in pancreatic β-cells.

【 授权许可】

CC BY-NC-ND   
© 2014 The Authors. Journal of Diabetes Investigation published by Asian Association of the Study of Diabetes (AASD) and Wiley Publishing Asia Pty Ltd

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