美迪西請回答為您講解GLP-1 作用機制。

GLP-1結合GLP-1R(1)后，GLP-1R在胰島β細胞中偶聯Gas蛋白，激活腺苷環化酶（AC），促使cAMP在細胞內含量升高，可激活蛋白激酶A(PKA)和cAMP調節的鳥嘌呤核苷酸交換因子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 可以關閉ATP依賴的鉀離子通道，使細胞膜去極化；還可以激活電壓依賴的鈣離子通道（VDCC）使鈣離子內流并產生動作電位，這些途徑最終都會刺激血糖依賴性胰島素的分泌。

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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