Effects of Ca antagonists, nifedipine, niludipine and verapamil, on endocrine function of the pancreas.

To study the effects of two Ca antagonists, nifedipine and niludipine, on insulin and glucagon secretion, experiments were performed using an in situ local circulation of the canine pancreas. The test drugs were injected into the pancreatic artery in three graded doses (5, 10 and 100 nmoles/kg) during arginine infusion, and blood samples were taken from the pancreatic vein. Verapamil, 10, 100 and 1,000 nmoles/kg, administered in the same way, was used as a control drug. Nifedipine, 5 to 100 nmoles/kg, decreased plasma insulin (IRI) and increased plasma glucagon (IRG) in the pancreatic vein, but caused no marked changes of blood glucose levels in five dogs. Niludipine, 5 to 100 nmoles/kg, injected into the pancreatic artery of 5 dogs, did not change blood glucose levels, but decreased slightly plasma IRI in the pancreatic vein and increased plasma IRG. Verapamil administered to 5 dogs caused no remarkable change of blood glucose or plasma IRG but decreased plasma IRI slightly. The maximum secretion of insulin was significantly lowered by nifedipine and niludipine, and that of pancreatic glucagon markedly increased by niludipine. The experiments revealed that Ca antagonists inhibit insulin secretion, and increase glucagon, and proved that calcium plays an important role in the A cell function of the pancreas.