The role of metabolism in the control of cyclic AMP efflux, cyclic AMP content, and insulin secretion from rat islets of Langerhans.

Glucose, alpha-ketoisocaproate, and N-acetylglucosamine all initiate insulin release and stimulate cyclic AMP efflux and cyclic AMP accumulation. Mannoheptulose inhibited these islet responses to glucose but not to N-acetylglucosamine or alpha-ketoisocaproate. On the other hand, menadione inhibited these responses to all three secretagogues. Nicotinamide enhanced the insulin release due to glucose and alpha-ketoisocaproate and also enhanced cyclic AMP efflux and intracellular cyclic AMP accumulation. N-acetylglucosamine-mediated insulin release, cyclic AMP efflux, and cyclic AMP accumulation were unaffected by nicotinamide. These results suggest that the metabolic state of the islet is a primary determinant of the ability of a secretagogue to raise cyclic AMP efflux and intracellular cyclic AMP, and these actions may be mediated in part by alterations in the redox state of the pyridine nucleotide system.