P2Y purinergic receptor-regulated insulin secretion is mediated by a cAMP/Epac/Kv channel pathway.
P2Y purinergic receptor-regulated insulin secretion is mediated by a cAMP/Epac/Kv channel pathway.
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DOI：
10.1016/j.bbrc.2015.03.121
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发表时间：
2015-05
影响因子：
3.1
通讯作者：
Yi Zhang;Qing Guo;Xiaodong Li;Jingying Gao;Yunfeng Liu;Jing Yang;Qingshan Li
中科院分区：
文献类型：
--
作者：
Yi Zhang;Qing Guo;Xiaodong Li;Jingying Gao;Yunfeng Liu;Jing Yang;Qingshan Li
增强胰岛素分泌是2型糖尿病（T2 D）的主要治疗方法。P2 Y嘌呤能受体（P2 YR）的激活以葡萄糖依赖性方式引起胰岛素分泌增强，使其成为T2 D的有希望的治疗靶点。在这里，我们表明，激活P2 YR，以加强胰岛素分泌介导的腺苷酸环化酶/环AMP（cAMP）和下游效应，交换蛋白直接激活cAMP（Epac），导致抑制电压依赖性钾（KV）通道。P2 YR介导的Kv通道抑制导致动作电位时程延长，进而提高细胞内Ca 2+水平和胰岛素分泌。综上所述，数据表明cAMP/Epac/Kv通道途径介导P2 YR调节的胰岛素分泌，这可能对T2 D具有重要的治疗意义。
Enhancement of insulin secretion is a major therapeutic approach for type 2 diabetes (T2D). Activation of P2Y purinergic receptor (P2YR) causes potentiation of insulin secretion in a glucose-dependent manner, making it a promising therapeutic target for T2D. Here we show that activation of P2YR to potentiate insulin secretion is mediated by adenylyl cyclase/cyclic AMP (cAMP) and the downstream effector, exchange protein directly activated by cAMP (Epac), leading to inhibition of voltage-dependent potassium (Kv) channels. P2YR-mediated Kv channel inhibition results in prolongation of action potential duration, and in turn elevates intracellular Ca2+level and insulin secretion. Taken together, the data indicate that cAMP/Epac/Kv channel pathway mediates P2YR-regulated insulin secretion, which may have important therapeutic implications for T2D.