PI3K is involved in P2Y receptor-regulated cAMP/Epac/Kv channel signaling pathway in pancreatic beta cells
PI3K is involved in P2Y receptor-regulated cAMP/Epac/Kv channel signaling pathway in pancreatic beta cells
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PI3K参与胰腺β细胞中P2Y受体调节的cAMP/Epac/Kv通道信号通路
DOI：
10.1016/j.bbrc.2015.08.057
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发表时间：
2015
影响因子：
3.1
通讯作者：
Yang Jing
中科院分区：
文献类型：
--
作者：
Zhang Yi;Wang Hui;Guo Qing;Li Xiaodong;Gao Jingying;Liu Yunfeng;Yang Caihong;Niu Longgang;Yang Jing
P2Y 受体 (P2YR) 是嘌呤能 G 蛋白偶联受体家族，可以受到细胞外核苷酸的刺激。在胰腺 β 细胞中，P2YR 的激活早已被证明可以以葡萄糖依赖性方式刺激胰岛素分泌。之前，我们报道了 P2YR 调节的胰岛素分泌是由 cAMP/Epac/Kv 通道途径介导的。然而，Epac 和 Kv 通道在 P2YR 调节胰岛素分泌中的相互作用仍不清楚。在本研究中，我们使用膜片钳技术和胰岛素分泌测定来研究可能将 Epac 与 P2YR 激活诱导的 Kv 通道抑制联系起来的潜在分子。我们发现磷脂酰肌醇 3-激酶介导 P2YR 调节的胰岛素分泌，是 Epac 和 Kv 通道之间的关键介质。
P2Y receptors (P2YR) are a family of purinergic G protein-coupled receptors, which could be stimulated by extracellular nucleotides. In pancreatic β cells, activation of P2YR has long been shown to stimulate insulin secretion in a glucose-dependent manner. Previously, we reported that P2YR-modulated insulin secretion is mediated by a cAMP/Epac/Kv channel pathway. However, the interaction between Epac and the Kv channel in P2YR-modulated insulin secretion remains unclear. In this study, we used patch-clamp technique and insulin secretion assay to investigate the potential molecules that may link Epac to Kv channel inhibition induced by P2YR activation. We identified that phosphatidylinositide 3-kinase, which mediates P2YR-regulated insulin secretion, is a critical mediator between Epac and the Kv channel.