Forskolin-Induced Activation of Adenylate Cyclase, Cyclic Adenosine Monophosphate Production and Insulin Release in Rat Pancreatic Islets*

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Abstract
Forskolin activated adenylate cyclase in rat islet homogenates and stimulated cAMP production in intact islets incubated in the absence or presence of either D-glucose or Ca2+. Forskolin failed to affect D-[U-14C]glucose oxidation, glucosestimulated net 45Ca uptake, or basal insulin release, but enhanced insulin secretion evoked by either nutrients (D-glucose, 2-ketoisocaproate, L-leucine alone or in combination with Lglutamine), or nonnutrient secretagogues (12-O-tetradecanoylphorbol-13-acetate, Ba2+ alone or in combination with theophylline). Forskolin stimulated insulin release from islets incubated in the presence of glucose but in the absence of Ca2+. These findings confirm that a marked increase in cAMP production is not sufficient to cause sustained insulin release. They also suggest that the enhancing action of endogenous cAMP upon insulin release does not depend on a facilitation of Ca2+ influx into islet cells. (Endocrinology115: 2015–2020, 1984)