Mechanisms of GLP-1

After activation by full agonists such as GLP-1,GLP-1R(1)couples with Gas activates adenolate cyclase(AC),and causes the accumulation of increasing cAMP levels, protein kinase A（PKA） and the exchange protein directly activated by cAMP-2(Epac-2) are also activated. PKA and Epac-2 trigger the closure of KATP and KV channels,which depolarizes the cell membrane opens voltage-dependent Calcium channels(VDCC) and causes Calcium influx and the promotion of insulin secretion by the islet beta cells.