Mediation of insulin release by cGMP and cAMP in a starved animal model

Islets isolated from fed rats released insulin in response to glucose, 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP), but not to 8-bromoinosine 3',5'-cyclic monophosphate. Starving rats for 48 h significantly diminished insulin release from islets in response to these agents, and lowered endogenous levels of cGMP and cAMP. The analogs of cGMP and cAMP potentiated the glucose response in a dose-dependent manner in islets from starved rats, whereas in fed rat islets the cyclic nucleotide analogs did not potentiate glucose-stimulated insulin release. Sodium nitroprusside, which enhances endogenous cGMP levels in islets, also enhanced the glucose response in islets from starved rats. Mannoheptulose inhibited glucose and 8-Br-cGMP-stimulated insulin release, but not 8-Br-cAMP-stimulated release. These results suggest that the impaired glucose response of islets from starved animals is in part due to diminished levels of cyclic nucleotides, and that the role(s) of cGMP in insulin secretion may include enhancement of glucose metabolism.