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GLP-1结合GLP-1R(1)后，GLP-1R在胰岛β细胞中偶联Gas蛋白，激活腺苷环化酶（AC），促使cAMP在细胞内含量升高，可激活蛋白激酶A(PKA)和cAMP调节的鸟嘌呤核苷酸交换因子2（Epac-2）。

After activation by full agonists such as GLP-1,GLP-1R(1)  couples with Gas activates adenolate cyclase(AC),and causes the accumulation of cAMP.With increasing cAMP levels, protein kinase A（PKA） and the exchange protein directly activated by cAMP-2(Epac-2) are also activated.

PKA 和 Epac-2 可以关闭ATP依赖的钾离子通道，使细胞膜去极化；还可以激活电压依赖的钙离子通道（VDCC）使钙离子内流并产生动作电位，这些途径最终都会刺激血糖依赖性胰岛素的分泌。

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

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