New concept of the glucagon-like peptide-1 signaling pathway on pancreatic insulin secretion.

The intracellular glucagon-like peptide-1 (GLP-1) signaling pathway, which involves cyclic adenosine monophosphate (cAMP), exchange protein directly activated by cAMP, cAMP-dependent protein kinase A (PKA) and adenosine triphosphate-sensitive potassium channels, has been widely accepted as a common mechanism of GLP-1-stimulated insulin secretion. Recent studies showed that a stimulatory effect of GLP-1 is also mediated by cAMP/PKA-independent mechanisms, including induction of Gαq activity followed by phospholipase C and protein kinase C activation. Furthermore, transient receptor potential 4 and transient receptor potential 5 channels play a role in protein kinase C-induced Ca2+ current. This pathway is a unique action mechanism of GLP-1 at physiologically low concentrations.