Expression of cAMP-regulated guanine nucleotide exchange factors in pancreatic beta-cells

The insulinotropic hormone glucagon-like peptide-1 (GLP-1) binds to a Gs-co upled receptor on pancreatic beta -cells and potentiates glucose-induced in sulin secretion, insulin gene transcription, and beta -cell growth. These s timulatory effects have been attributed to the elevation of intracellular c AMP levels, though it is now apparent that some stimulatory effects of GLP- 1 occur independently of the cAMP-mediated activation of protein kinase A ( PKA). The nature of this alternative, PKA-independent signaling pathway rem ains unknown. Here we present evidence for the expression of type 1 and typ e 2 cAMP-regulated guanine nucleotide exchange factors (cAMP-GEFs) in beta -cells. GEFs are activated by their binding of cAMP. Because cAMP-GEFs acti vate Ras/MAPK proliferation signaling pathways, they may play an important role in PKA-independent, GLP-1-mediated, signaling pathways in the regulati on of beta -cell growth and differentiation. (C) 2000 Academic Press.