Activity of the calcium-sensing receptor influences blood glucose and insulin levels in rats

The calcium-sensing receptor (CaR) has been found not only in parathyroid glands but also in other tissues, e.g. in β cells of the pancreatic islets. Therefore, CaR might likely mediate the mechanism of insulin secretion. The present study was designed to examine the in vivo effects of R-568, a CaR agonist, and NPS2143, a CaR inhibitor, on plasma insulin and blood glucose concentrations. Wistar rats, after fasting for 14 h before the experiment, were anesthetized with inactin and loaded ip with 1 g/kg glucose. 20, 120 and 180 min after iv R-568 administration, plasma insulin increased markedly (by approximately 30%), in glucose-loaded rats, as compared to the control animals. S imultaneously, 180 min after R-568 administration, a significant drop by approximately 12% in blood glucose was observed. In contrast, administration of R-568 in rats not given glucose, did not influence the blood glucose or plasma insulin concentrations vs. the control group. Administration of NPS2143 increased the blood glucose level markedly (by about 18% vs. control group) at 180 and 210 min of the experiment. Simultaneously, a significant decrease of insulin concentration was observed vs. control group (by about 18 and 23%, respectively). We suggest that modulation of the CaR activity may participate in the mechanisms which mediate insulin secretion in rats.