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Robust GLP-1 secretion by basic L-amino acids does not require the GPRC6A receptor.

Christoffer Clemmensen1,2, Christinna V Jørgensen1, Sanela Smajilovic1

  • 1Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.

Diabetes, Obesity & Metabolism
|December 13, 2016
PubMed
Summary

The G protein-coupled receptor GPRC6A does not appear essential for L-amino acid-induced glucagon-like peptide 1 (GLP-1) secretion. L-arginine and L-ornithine effectively stimulate GLP-1 release independently of GPRC6A.

Keywords:
GLP-1 releaseGPRC6AL-arginineL-ornithinemouse pharmacology

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Area of Science:

  • Endocrinology
  • Metabolism
  • Gastroenterology

Background:

  • The G protein-coupled receptor GPRC6A is implicated as a sensor for basic L-amino acids, potentially linking nutrient intake to hormonal signals.
  • The precise role of GPRC6A in mediating L-amino acid-stimulated glucagon-like peptide 1 (GLP-1) secretion remains incompletely understood.

Purpose of the Study:

  • To investigate whether the GPRC6A receptor is indispensable for L-amino acid-induced GLP-1 secretion.
  • To determine the specific contribution of GPRC6A to the effects of L-arginine and L-ornithine on GLP-1 release in vivo.

Main Methods:

  • Oral gavage administration of GPRC6A ligands (L-arginine and L-ornithine) to GPRC6A knock-out (KO) and wild-type (WT) littermate mice.
  • Measurement of total plasma GLP-1 levels at various time points (15, 30, and 60 minutes) post-administration.

Main Results:

  • Both L-arginine and L-ornithine significantly increased plasma GLP-1 levels in both KO and WT mice at 15 minutes.
  • L-arginine demonstrated sustained GLP-1 elevation up to 60 minutes in both genotypes.
  • GLP-1 secretion in KO mice was attenuated at 30 and 60 minutes, failing to reach statistical significance for L-ornithine.

Conclusions:

  • L-arginine is confirmed as a potent GLP-1 secretagogue, with its primary effect occurring independently of the GPRC6A receptor.
  • This study provides the first evidence that L-ornithine also potently stimulates GLP-1 release in vivo, irrespective of GPRC6A signaling.