title: Robust GLP-1 secretion by basic L-amino acids does not require the GPRC6A receptor.
abstract: The G protein-coupled receptor GPRC6A (GPCR, Class C, group 6, subtype A) has been proposed to be a sensor for basic L-amino acids that are hypothesized to translate ingestive behaviour to endocrine information. However, the contribution of the GPRC6A receptor to L-amino acid-induced glucagon-like peptide 1 (GLP-1) secretion is unclear. Therefore, to discover whether the GPRC6A receptor is indispensible for amino acid-induced secretion of GLP-1, we treated, with oral gavage, GPRC6A knock-out (KO) and wild-type (WT) littermate mice with GPRC6A ligands (L-arginine and L-ornithine) and assessed GLP-1 levels in circulation. We found that oral administration of both L-arginine and L-ornithine significantly increased total plasma GLP-1 levels to a similar level in GPRC6A KO and WT mice 15 minutes after gavage (both amino acids) and accumulated up to 60 minutes after gavage (L-arginine). Conversely, GLP-1 secretion at the 30- and 60-minute time points in the KO mice was attenuated and did not reach statistical significance. In summary, these data confirm that L-arginine is a potent GLP-1 secretagogue and show that the main effect occurs independently of GPRC6A. In addition, this is the first study to show that also L-ornithine powerfully elicits GLP-1 release in vivo.
authors.affiliation: Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.|Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Clemmensen
authors.affiliation: Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christinna V
authors.initials: CV
authors.lastname: Jørgensen
authors.affiliation: Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sanela
authors.initials: S
authors.lastname: Smajilovic
authors.affiliation: Faculty of Health and Medical Sciences, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Bräuner-Osborne
mesh_terms: D024361:Amino Acids, Basic / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009952:Ornithine / Q000008:administration & dosage / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*
chemical_list: D024361:Amino Acids, Basic; C515750:GPRC6A protein, mouse; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D052216:Glucagon-Like Peptide 1; D001120:Arginine; D009952:Ornithine
keywords: 
  GLP-1 release; 
  GPRC6A
  ; 
  L-arginine; 
  L-ornithine; mouse pharmacology