Verapamil prevents the effect of calcium-sensing receptor activation on the blood glucose and insulin levels in rats

• Published in: Pharmacological reports 2019-06, Vol.71 (3), p.478-484
• Main Authors: Szczoczarz, Anna, Marchwińska, Aleksandra, Dyś, Aleksandra, Boblewski, Konrad, Lehmann, Artur, Lewko, Barbara, Rybczyńska, Apolonia
• Format: Article
• Language: English
• Subjects: Animals; Blood calcium concentration; Blood Glucose - drug effects; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Drug Safety and Pharmacovigilance; Glucose - metabolism; Insulin - metabolism; Insulin Secretion - drug effects; Male; Naphthalenes - pharmacology; NPS 2143; Original Article; Pancreas; Pharmacotherapy; Pharmacy; Phenethylamines - pharmacology; Propylamines - pharmacology; R-568; Rats; Rats, Wistar; Receptors, Calcium-Sensing - metabolism; Verapamil - pharmacology
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/j.pharep.2019.01.004

The Ca2+ triggered insulin exocytosis in β cells of the pancreatic islets may be the result of Ca2+ influx through L-type voltage dependent calcium channels (VDCC) localized in the plasma membrane, as well as of liberation of Ca2+ from intracellular storages, induced by activation of the calcium receptor (CaR) coupled with the PLC enzyme present in the pancreatic islets. The present study was designated to determine, in in vivo experiments, the effects of CaR activation by R-568 and inhibition of the receptor by NPS 2143 on the plasma glucose and insulin levels in the presence of verapamil, a calcium channel blocker. Wistar rats, after fasting for 14 h before the experiment, were anesthetized with inactin and loaded ip with 1 g/kg glucose. In comparison to the control group, the verapamil-induced blockade of the calcium channels in glucose loaded animals increased the blood glucose level and decreased the insulin level, whereas CaR activation with R-568 induced opposite effects. However, in the presence of verapamil, R-568 did not change the concentration of glucose or insulin versus the control animals. Verapamil infusion did not alter elevated glucose concentration in the NPS 2143 animals. At the same time, verapamil reduced the plasma insulin level and potentiated the drop of insulin concentration induced by NPS 2143. The observations suggest that under the in vivo conditions, calcium channel blockade may prevent changes in the blood glucose and insulin concentrations induced by the CaR activation.