Long-term and short-term effects of calcium, verapamil and diazoxide on biosynthesis and release of (pro-) insulin in isolated islets of rat pancreas.

Abstract

Abstract. Glucose-induced release and biosynthesis of insulin can be influenced independently during short-term incubations of isolated pancreatic islets. We studied whether such a dissociation between synthesis and release is still retained after a longer period of islet culture. Media varying in calcium concentration (0, 0.8, 2.5, 5.0 mm), verapamil (8 μm) or diazoxide (100 μg/ml) were used in short-term incubations for 2 h and during 38 h of islet culture at 2 mg/ml glucose. In the short-term experiments, the increase in calcium concentration caused a stepwise augmentation of insulin release but a gradual decrease in (pro-)insulin synthesis; verapamil and diazoxide markedly diminished insulin secretion, whereas hormone biosynthesis was found unchanged. Culture of islets with calcium omission, verapamil or diazoxide resulted also in a reduced insulin release during the 38 h of cultivation. After culture, insulin release was not different from the controls any more. (Pro-)Insulin biosynthesis, however, was now significantly diminished in islets cultured before with verapamil and diazoxide; following culture in calcium-free medium biosynthesis was also relatively decreased compared to the values obtained in the acute short-term experiments. It appears from these results that the pharmacological inhibitors of insulin release tested in vitro do no longer influence release and biosynthesis of insulin independently after a longer culture period, in contrast to their short-term effects.