title: Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor T1R3.
abstract: 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.
authors.affiliation: Institute for Molecular & Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohtsu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagasawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibata
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
mesh_terms: D019325:3-O-Methylglucose / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013386:Succinates / Q000494:pharmacology; D013395:Sucrose / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D007328:Insulin; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D013386:Succinates; C431926:taste receptors, type 1; D019325:3-O-Methylglucose; D013395:Sucrose; D000255:Adenosine Triphosphate; C026285:trichlorosucrose; C039138:methylsuccinic acid; D005947:Glucose