title: GPRC6A mediates the effects of L-arginine on insulin secretion in mouse pancreatic islets.
abstract: L-arginine (l-Arg) is an insulin secretagogue, but the molecular mechanism whereby it stimulates insulin secretion from β-cells is not known. The possibility that l-Arg regulates insulin secretion through a G protein-coupled receptor (GPCR)-mediated mechanism is suggested by the high expression of the nutrient receptor GPCR family C group 6 member A (GPRC6A) in the pancreas and TC-6 β-cells and the finding that Gprc6a(-/]minus]) mice have abnormalities in glucose homeostasis. To test the direct role of GPRC6A in regulating insulin secretion, we evaluated the response of pancreatic islets derived from Gprc6a(-/]minus]) mice to L-Arg. We found that the islet size and insulin content were decreased in pancreatic islets from Gprac6a(-/]minus]) mice. These alterations were selective for β-cells, because there were no abnormalities in serum glucagon levels or glucagon content of islets derived from Gprac6a(-/]minus]) mice. Significant reduction was observed in both the pancreatic ERK response to L-Arg administration to Gprc6a(-/]minus]) mice in vivo and L-Arg-induced insulin secretion and production ex vivo in islets isolated from Gprc6a(-/]minus]) mice. L-Arg stimulation of cAMP accumulation in isolated islets isolated from Gprc6a(-/]minus]) mice was also diminished. These findings suggest that l-Arg stimulation of insulin secretion in β-cells is mediated, at least in part, through GPRC6A activation of cAMP pathways.
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. mpi@uthsc.edu
authors.forename: Min
authors.initials: M
authors.lastname: Pi
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Wu
authors.forename: Nataliya I
authors.initials: NI
authors.lastname: Lenchik
authors.forename: Ivan
authors.initials: I
authors.lastname: Gerling
authors.forename: L Darryl
authors.initials: LD
authors.lastname: Quarles
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: C515750:GPRC6A protein, mouse; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D005934:Glucagon; D001120:Arginine; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose