Abstract
GPRC6A is a seven-transmembrane receptor activated by a wide range of l-α-amino acids, most potently by l-arginine and other basic amino acids. The receptor is broadly expressed, but its exact physiological role remains to be elucidated. It is well established that l-arginine stimulates insulin secretion; therefore, the receptor has been hypothesized to have a role in regulating glucose metabolism. In this study, we demonstrate that GPRC6A is expressed in islets of Langerhans, but activation of the receptor by l-arginine did not stimulate insulin secretion. We also investigated central metabolic parameters in GPRC6A knockout mice compared with wildtype littermates and found no difference in glucose metabolism or body fat percentage when mice were administered a standard chow diet. In conclusion, our data do not support a role for GPRC6A in l-arginine-induced insulin release and glucose metabolism under normal physiological conditions.
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Acknowledgments
We would like to thank Jens Pedersen for valuable inputs for the study. This work was supported by the UNIK: Food, Fitness and Pharma for health and disease research programme, the Danish Medical Research Council and the Drug Research Academy.
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Supp. Fig. 1 Insulin secretion after intravenous injection of l-arginine in vivo.l-arginine (0.05 g/kg) or NaCl (control) was injected intravenously in a tail vein in ad libitum-fed male GPRC6A KO and WT mice. Blood samples were drawn from the retrobulbar intraorbital capillary plexus before (0 min) and 1 min, 2 min, and 5 min after the injection into EDTA coated blood collection tubes, and plasma separated by centrifugation.Data are mean ± SEM, n = 6-10 per group; * P < 0.05 (PPTX 80 kb)
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Smajilovic, S., Clemmensen, C., Johansen, L.D. et al. The l-α-amino acid receptor GPRC6A is expressed in the islets of Langerhans but is not involved in l-arginine-induced insulin release. Amino Acids 44, 383–390 (2013). https://doi.org/10.1007/s00726-012-1341-8
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DOI: https://doi.org/10.1007/s00726-012-1341-8