| First Author | Pi M | Year | 2012 |
| Journal | Endocrinology | Volume | 153 |
| Issue | 10 | Pages | 4608-15 |
| PubMed ID | 22872579 | Mgi Jnum | J:191439 |
| Mgi Id | MGI:5461763 | Doi | 10.1210/en.2012-1301 |
| Citation | Pi M, et al. (2012) GPRC6A mediates the effects of L-arginine on insulin secretion in mouse pancreatic islets. Endocrinology 153(10):4608-15 |
| abstractText | L-arginine (l-Arg) is an insulin secretagogue, but the molecular mechanism whereby it stimulates insulin secretion from beta-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 beta-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 beta-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 beta-cells is mediated, at least in part, through GPRC6A activation of cAMP pathways. |
