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 Ca(2+) current. This pathway is a unique action mechanism of GLP‐1 at physiologically low concentrations.[Image: see text]