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

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Abstract
Glucose-induced release and biosynthesis of insulin can be influenced independently during short-term incubations of isolated pancreatic islets. Whether such a dissociation between synthesis and release is still retained after a longer period of islet culture was studied. Media varying in Ca concentration (0, 0.8, 2.5, 5.0 mM) verapamil (8 .mu.M) or diazoxide (100 .MU.g/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 Ca concentration caused a stepwise augmentation of insulin release but a gradual decrease in (pro-)insulin synthesis; verapamil and diazoxide markedly diminished insulin secretion; hormone biosynthesis was unchanged. Culture of islets with Ca 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 Ca free medium biosynthesis was also relatively decreased compared to the values obtained in the acute short-term experiments. Apparently, 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.