Forskolin, an Activator of Adenylate Cyclase, Stimulates Pancreatic Insulin, Glucagon, and Somatostatin Release in the Dog: Studies in Vitro*

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Abstract
Forskolin, a direct activator of adenylate cyclase, stimulates cAMP production in islet cells. The effects of forskolin on the release of somatostatin, glucagon, and insulin were studied using the isolated, perfused dog pancreas. It was found that concentrations ranging from 0.075 -1 .mu.M stimulated the secretion of somatostatin, glucagon, and insulin in a dose-related manner. The effects of 0.15 .mu.M anf of 0.6 .mu.M forskolin were modulated by the prevailing glucose level with higher D and B and lower A cell responses at high (11 mM) than at low (2.8 mM) or zero glucose. In the absence of extracellular Ca2+, forskolin (1 .mu.M) possessed no stimulatory effect on pancreatic hormone secretion. Perfusion of 1 .mu.M atropine, 1 .mu.M propranolol, and 1 .mu.M phentolamine had no effect on forskolin-mediated (0.3 .mu.M) hormone output from pancreas. The phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (25 .mu.M) elicited qualitatively similar hormone response to forskolin. In conclusion, the experiments demonstrate that forskolin is a potent, reversible, stimulus of pancreatic hormone secretion. Its effects are apparently not mediated via the sympathetic or parasympathetic nerve endings in pancreas. Forskolin may prove to be a valuable pharmacological tool in probing the role of the adenylate cyclase-cAMP system in pancreatic hormone secretion.