Regulation of Adenosine 3′,5′-Monophosphate Levels in the Pancreatic B Cell*

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Abstract
Poor glucose-induced insulin release from single purified B [beta] cells has been attributed, in part, to low cellular cAMP levels. Isolated B cells exhibit a markedly lower cAMP formation than B cells loged in intact islets and this deficiency may be caused by their separation from glucagon-containing A [alpha] cells. cAMP levels in purified B cells are rapidly and potently elevated by glucagon from 10-10 M on, reaching the values of islet B cells at 10-9 M. In contrast, exogenous glucagon stimulates cAMP formation in isolated islets only from 3.10-9 M on, suggesting that endogenously released glucagon is mainly responsible for the higher cAMP levels in islet B cells. Somatostatin counteracts glucagon-induced cAMP production in purified B cells, and, therefore, has also the potential to mediate and intraislet regulation of B cell functions. Neither insulin nor pancreatic polypeptide affect cAMP formation in pancreatic B cells. Glucose alone does not influence cAMP levels in purified B cells, but enhances glucagon-induced cAMP formation in these cells. The glucose-dependent increase in islet cAMP is therefore not considered as the nutrient-induced mediator for hormone release but as a minor amplification of the glucagon-dependent signal. Experiments on reaggregated islet cells permit the reconstruction of the events which regulate cAMP levels in isolated islets. A normal glucose-induced insulin release from intact islets requires the simultaneous synarchic participation of a nutrient-dependent and a hormone-dependent messenger system.