Protein kinase A-independent mechanism of cAMP in insulin secretion

Abstract

Although an increase in the intracellular calcium concentration is the primary signal in the regulation of insulin secretion, other intracellular signals are also important, adenosine 3′,5′-cyclic monophosphate (cAMP) being especially critical. cAMP is well known to potentiate glucose-induced insulin secretion. Until recently, the action of cAMP on insulin secretion was generally thought to be mediated exclusively by the activation of protein kinase A (PKA), which phosphorylates proteins associated with the secretory processes. However, accumulating evidence indicates that the cAMP-binding protein, cAMP-regulated guanine nucleotide exchange factor (cAMP-GEF)/exchange proteins activated directly by cyclic AMP (Epac), participates in a novel, PKA-independent mechanism of cAMP action in insulin secretion. cAMP compartmentation in pancreatic beta cells has been proposed to account for these distinct effects of cAMP signaling in insulin secretion. © 2008 Springer.