Cyclic AMP metabolism and insulin release in pancreatic islets of the rat Effects of agents which alter microtubular function

Abstract

In order to investigate the relationship between microtubular function, insulin release and islet cyclic AMP metabolism, the effects of 2H 2O, colchicine and vincristine were studied in rat islets prelabeled with [ 3H]adenine. Glucose-induced insulin secretion and efflux of cyclic [ 3H]AMP was markedly inhibited by 8–50% 2H 2O. At a higher concentration (75%), deuterated water still suppressed insulin release, while the inhibition of nucleotide release was abolished. Glucose-induced intra-islet cyclic [ 3H]AMP accumulation was augmented by 2H 2O progressively with time. With 75% 2H 2O, although efflux of cyclic AMP was no more inhibited, intra-islet accumulation of the nucleotide was still enhanced. The cyclic AMP efflux induced by cholera toxin, or a high concentration of 3-isobutyl-1-methylxanthine was suppressed and the intra-islet nucleotide accumulation was enhanced by 2H 2O. The latter effect tended to be less pronounced than when glucose was the stimulator. All the effects of 2H 2O on glocuse-stimulated islets were mimicked by incubating the tissue in H 2O at 28°C. Colchicine and vincristine had no significant effect on glucose-induced insulin release, and did not enhance the intra-islet cyclic [ 3H]AMP response; efflux of the nucleotide was, however, significantly inhibited. This pattern of response was shared with probenecid. Preincubation of islets with colchicine did not influence the subsequent effects of 2H 2O on insulin release and cyclic AMP metabolism. It is concluded that: (1) enhancement of intra-islet cyclic AMP accumulation by 2H 2O is not due to inhibition of the nucleotide efflux; (2) the effects on cyclic AMP metabolism described here are not exclusive for microtubular affecting agents and do not seem to be related to the microtubular system of the islet.