title: Glucose-Sensing Receptor T1R3: A New Signaling Receptor Activated by Glucose in Pancreatic β-Cells.
abstract: Subunits of the sweet taste receptors T1R2 and T1R3 are expressed in pancreatic β-cells. Compared with T1R3, mRNA expression of T1R2 is considerably lower. At the protein level, expression of T1R2 is undetectable in β-cells. Accordingly, a major component of the sweet taste-sensing receptor in β-cells may be a homodimer of T1R3 rather than a heterodimer of T1R2/T1R3. Inhibition of this receptor by gurmarin or deletion of the T1R3 gene attenuates glucose-induced insulin secretion from β-cells. Hence the T1R3 homodimer functions as a glucose-sensing receptor (GSR) in pancreatic β-cells. When GSR is activated by the T1R3 agonist sucralose, elevation of intracellular ATP concentration ([ATP]i) is observed. Sucralose increases [ATP]i even in the absence of ambient glucose, indicating that sucralose increases [ATP]i not simply by activating glucokinase, a rate-limiting enzyme in the glycolytic pathway. In addition, sucralose augments elevation of [ATP]i induced by methylsuccinate, suggesting that sucralose activates mitochondrial metabolism. Nonmetabolizable 3-O-methylglucose also increases [ATP]i and knockdown of T1R3 attenuates elevation of [ATP]i induced by high concentration of glucose. Collectively, these results indicate that the T1R3 homodimer functions as a GSR; this receptor is involved in glucose-induced insulin secretion by activating glucose metabolism probably in mitochondria.
authors.affiliation: Institute for Molecular & Cellular Regulation, Gunma University.
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Hamano
authors.forename: Johan
authors.initials: J
authors.lastname: Medina
authors.forename: Longfei
authors.initials: L
authors.lastname: Li
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagasawa
mesh_terms: D019325:3-O-Methylglucose / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013395:Sucrose / Q000031:analogs & derivatives* / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology; D013649:Taste
chemical_list: D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; D019325:3-O-Methylglucose; D013395:Sucrose; D000255:Adenosine Triphosphate; C026285:trichlorosucrose; D000242:Cyclic AMP; D005947:Glucose