Return of the glucoreceptor: Glucose activates the glucose‐sensing receptor T1R3 and facilitates metabolism in pancreatic β‐cells. Issue 3 (15th December 2014)

• Record Type: Journal Article
• Authors: Kojima, Itaru; Nakagawa, Yuko; Ohtsu, Yoshiaki; Hamano, Kunihisa; Medina, Johan; Nagasawa, Masahiro
• Is Part Of: Journal of diabetes investigation. Volume 6:Issue 3(2015:Jun.)
• Page Start: 256
• Page End: 263
• Publication Date: 2014-12-15
• Subjects: Glucose -- Insulin secretion -- Sweet taste receptor; Diabetes -- Periodicals; Diabetes -- Research -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462005
• DOI: 10.1111/jdi.12304
• Languages: English
• ISSNs: 2040-1116

Abstract

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. Abstract : A homodimer of T1R3 functions as the glucose‐sensing receptor in pancreatic beta‐cells. This receptor facilitates glucose metabolism and promotes insulin secretion induced by glucose.