Cyclic AMP and insulin release

The role of cyclic adenosine-3',5'-monophosphate (cAMP) for insulin secretion has been investigated. In isolated islets of Langerhans from the rat, glucose increases cAMP concomitant with insulin secretion. Stimulation of these two parameters is likewise reversible in parallel. The minimal and maximal concentrations of glucose eliciting cAMP and insulin responses are similar. Isomers and epimers of glucose influence insulin and cAMP in a parallel fashion as do sulfonylurea compounds (tolbutamide and glibenclamide). On the contrary, the time-dependent potentiation of glucose-induced insulin secretion is not accompanied by gross changes in cAMP. Reciprocally, in the absence of glucose islet cAMP can be markedly elevated by other agents (methyl xanthines, cholera toxin) without major insulin responses. The results indicate that metabolism of cAMP in the beta-cell is intimately linked to the glucose (and sulfonylurea) action on insulin secretion, although other factors influenced by the hexose are also necessary for the release process. The finding that the cAMP response is impaired in fasting, during the neonatal period and in diabetes mellitus (in the Chinese hamster) suggests an important role for the nucleotide in physiological and pathophysiological states characterized by decreased insulin release.