title: Amino acid taste receptor regulates insulin secretion in pancreatic β-cell line MIN6 cells.
abstract: Amino acids such as L-glutamate and L-arginine are potent stimuli for insulin secretion from pancreatic β-cells. However, the precise molecular mechanisms of amino acid-induced insulin secretion have only partly understood. In this study, we show here that mouse pancreatic β-cell line MIN6 cells expressed amino acid taste receptor (heterodimer of type 1 taste G protein-coupled receptor member 1 and member 3; Tas1R1 and Tas1R3, respectively). We found that administration of L-glutamate or L-arginine to MIN6 cells caused the increase in free intracellular concentrations of both inositol-1,4,5-triphosphate (IP(3)) and Ca(2+) , and umami substance inocinate enhanced the effects of l-glutamate. Effects of amino acids on intracellular IP(3) and Ca(2+) concentration were diminished by application of lactisole, a Tas1R3 receptor antagonist. Furthermore, we investigated the effect of amino acids on the insulin release from MIN6 cells by both ELISA and total internal reflection fluorescence microscopy. Application of L-glutamate or L-arginine significantly increased the release of insulin, whereas inhibited by the application of lactisole. Based on these findings, we propose that heterodimer of Tas1R1 and Tas1R3 is the fundamental receptor for the sensing amino acids and regulates the amino acid-induced insulin secretion in pancreatic β-cells.
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Oya
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Sato
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuboi
mesh_terms: D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D001555:Benzene Derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D031541:Fluorescence Resonance Energy Transfer; D015870:Gene Expression; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D055503:Protein Multimerization; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013649:Taste
chemical_list: D000596:Amino Acids; D001555:Benzene Derivatives; D007328:Insulin; D008164:Luminescent Proteins; D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D018698:Glutamic Acid; D015544:Inositol 1,4,5-Trisphosphate; D001120:Arginine; C524407:GNAT3 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins; D002118:Calcium; C495512:lactisole