Robust GLP-1 secretion by basic L-amino acids does not require the GPRC6A receptor
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Robust GLP-1 secretion by basic L-amino acids does not require the GPRC6A receptor. / Clemmensen, Christoffer; Jørgensen, Christinna V; Smajilovic, Sanela; Bräuner-Osborne, Hans.
In: Diabetes, Obesity and Metabolism, Vol. 19, No. 4, 2017, p. 599-603.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Robust GLP-1 secretion by basic L-amino acids does not require the GPRC6A receptor
AU - Clemmensen, Christoffer
AU - Jørgensen, Christinna V
AU - Smajilovic, Sanela
AU - Bräuner-Osborne, Hans
N1 - This article is protected by copyright. All rights reserved.
PY - 2017
Y1 - 2017
N2 - 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 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 probe if 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 were 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.
AB - 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 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 probe if 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 were 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.
U2 - 10.1111/dom.12845
DO - 10.1111/dom.12845
M3 - Journal article
C2 - 27943578
VL - 19
SP - 599
EP - 603
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 4
ER -
ID: 170073566