GPRC6A mediates the effects of L-arginine on insulin secretion in mouse pancreatic islets

Min Pi, Yunpeng Wu, Nataliya I. Lenchik, Ivan Gerling, L. Darryl Quarles

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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.

Original languageEnglish (US)
Pages (from-to)4608-4615
Number of pages8
JournalEndocrinology
Volume153
Issue number10
DOIs
StatePublished - Oct 1 2012

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Islets of Langerhans
Arginine
Insulin
G-Protein-Coupled Receptors
Glucagon
Pancreas
Homeostasis
Glucose
Food
Serum

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

GPRC6A mediates the effects of L-arginine on insulin secretion in mouse pancreatic islets. / Pi, Min; Wu, Yunpeng; Lenchik, Nataliya I.; Gerling, Ivan; Quarles, L. Darryl.

In: Endocrinology, Vol. 153, No. 10, 01.10.2012, p. 4608-4615.

Research output: Contribution to journalArticle

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