Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor T1R3

[摘要] References(22)Cited-By(9)A homodimer of taste type 1 receptor 3 (T1R3) functions as a sweet taste-sensing receptor in pancreatic β-cells.This receptor is activated by various sweet molecules including sugars such as glucose.To determine the role of this receptor in glucose-induced insulin secretion, we addressed whether or not this receptor modulates glucose metabolism in MIN6 cells.We measured changes in intracellular ATP ([ATP]i) in MIN6 cells expressing luciferase.Sucralose, an agonist of T1R3, induced immediate and sustained elevation of [ATP]i in the presence of 5.5 mM glucose.The effect of sucralose was dose-dependent and, at 5 mM, was greater than that induced by 25 mM glucose.In contrast, carbachol, GLP-1 or high concentration of potassium did not reproduce the sucralose action.Sucralose facilitated the increase in [ATP]i induced by a mitochondrial fuel methylsuccinate, and potentiated glucose-induced elevation of [ATP]i.Administration of a non-metabolizable glucose analogue, 3-O-methylglucose, which acts as an agonist of T1R3, induced a small and transient increase in [ATP]i.3-O-Methylglucose augmented elevation of [ATP]i induced by methylsuccinate, and also enhanced glucose-induced increase in [ATP]i.Knock down of T1R3 by using shRNA attenuated [ATP]i-response to high concentration of glucose and also reduced the glucose-induced insulin secretion.These results indicate that activation of the homodimer of T1R3 facilitates the metabolic pathway in mitochondria and augments ATP production.The results obtained by using 3-O-methylglucose suggest that glucose, by acting on the homodimer of T1R3, promotes its own metabolism.

[学科分类] 内分泌与代谢学

[关键词] Insulin;Pancreatic β-cell;Glucose;Sweet taste receptor;ATP