MECHANISM FOR GLP-1

GLP-1 action is mediated by binding to a specific, seven-transmembrane G-protein coupled receptor (GLP-1 receptor) that is coupled positively to the adenylyl cyclase (AC) system. Ligand activation of G-alpha sub unit of the GLP-1 receptor stimulates AC, which leads to an increase in intracellular c-AMP and activation of protein kinase A (PKA). GLP-1acts directly through c-AMP-PKA pathway to enhance and sensitize beta-cells to glucose stimulated insulin secretion. Glucose metabolism in the beta-cell causes an increase in the concentration of ATP and rises the cytoplasmic ATP: ADP ratio, which leads to depolarization of the plasma membrane following closure of ATP sensitive k+channels.This permits opening of voltage dependent L-type Ca+2channel s and increase cytosolic Ca+2 , which triggers fusion of insulin containing secretory vesicles to the plasma membrane.Exocytosis of insulin follows rapidly.