Akt Signals Upstream of L-Type Calcium Channels to Optimize Insulin Secretion
Akt Signals Upstream of L-Type Calcium Channels to Optimize Insulin Secretion
复制标题
Akt 向 L 型钙通道上游发出信号以优化胰岛素分泌
DOI：
10.1097/mpa.0b013e31822363a9
复制
发表时间：
2012
期刊：
影响因子：
2.9
通讯作者：
Shao
中科院分区：
文献类型：
--
作者：
Xiuli Cui;Guang Yang;M. Pan;Xiao;Shao
目的丝氨酸/苏氨酸蛋白激酶Akt和电压门控L型钙通道在葡萄糖刺激的胰岛素分泌中起重要作用。Akt募集L型钙通道并将其维持在质膜上。本研究的目的是表征L型钙通道在葡萄糖刺激的胰岛素分泌中介导Akt信号的作用。方法采用标准胰岛素放射免疫分析法测定大鼠胰岛和INS-1胰腺细胞的胰岛素分泌。结果Akt抑制剂不仅能有效抑制葡萄糖刺激的胰岛素分泌，还能抑制钾离子去极化刺激的胰岛素分泌，后者主要依赖于电压门控钙通道介导的Ca 2+内流，而不涉及葡萄糖代谢。同样地，Akt抑制也减少葡萄糖刺激的和钾去极化刺激的INS-1细胞的胰岛素分泌。重要的是，L型钙通道的药理学消融部分阻断了Akt抑制诱导的葡萄糖刺激的胰岛素分泌减少，但完全阻止了钾去极化诱导的INS-1细胞胰岛素释放。此外，Akt抑制不影响钙离子载体A23187诱导的INS-1细胞的胰岛素分泌，这在不涉及L型钙通道的情况下发生。结论Akt在L-型钙通道上游调控葡萄糖刺激的胰岛素分泌。缩写CaV -电压门控钙
Objectives Both the serine/threonine protein kinase Akt and the voltage-gated L-type calcium channel act as important players in glucose-stimulated insulin secretion. Akt recruits the L-type calcium channel to and maintains them in the plasma membrane. This study aimed to characterize the role of L-type calcium channels in mediation of Akt signaling in glucose-stimulated insulin secretion. Methods Insulin secretion was evaluated in rat pancreatic islets and INS-1 pancreatic &bgr; cells by a standard insulin radioimmunoassay. Results Akt inhibition effectively abrogates not only glucose-stimulated but also potassium depolarization-stimulated insulin secretion from rat islets, the latter critically relying on the voltage-gated calcium channel-mediated Ca2+ influx without involvement of glucose metabolism. Likewise, Akt inhibition also reduces both glucose-stimulated and potassium depolarization–stimulated insulin secretion from INS-1 cells. Importantly, pharmacological ablation of L-type calcium channels partially blocks Akt inhibition–induced reduction in glucose-stimulated insulin secretion but completely prevents that in potassium depolarization–evoked insulin release from INS-1 cells. Furthermore, Akt inhibition does not influence calcium ionophore A23187-induced insulin secretion from INS-1 cells, which occurred without involvement of L-type calcium channels. Conclusions Akt signals upstream of L-type calcium channels to optimize glucose-stimulated insulin secretion. Abbreviations CaV - voltage-gated calcium
DOI：
10.1172/jci20016
发表时间：
2004-10
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
E. Bernal-Mizrachi;S. Fátrai;James D. Johnson;M. Ohsugi;K. Otani;Zhi-qiang Han;K. Polonsky;M. Permutt
通讯作者：
E. Bernal-Mizrachi;S. Fátrai;James D. Johnson;M. Ohsugi;K. Otani;Zhi-qiang Han;K. Polonsky;M. Permutt