AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration.
AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration.
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DOI：
10.1371/journal.pone.0064633
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Terauchi Y
中科院分区：
文献类型：
--
作者：
Tajima K;Shirakawa J;Togashi Y;Inoue H;Sato K;Orime K;Ito Y;Kaji M;Sakamoto E;Nakamura A;Aoki K;Goshima Y;Atsumi T;Terauchi Y
尽管最近发现二甲双胍可增强胰腺β细胞中肠促胰岛素受体（GLP-1和GIP受体）的表达，但二甲双胍靶点AMP活化蛋白激酶（AMPK）在胰腺β细胞中的确切作用仍存在争议。本研究探讨AMPK对胰岛肠促胰岛素受体表达的调节作用。随着葡萄糖浓度的增加，小鼠胰岛中AMPK的磷酸化水平降低。我们发现肠促胰岛素受体的表达在钟形响应葡萄糖;肠促胰岛素受体的表达在分离的胰岛中显示出较高的水平下，在中等葡萄糖浓度（11.1 mM）下比在低葡萄糖浓度（2.8 mM），但在高葡萄糖浓度（22.2 mM）下被抑制。在低葡萄糖浓度下，AMPK抑制剂和DN-AMPK表达的处理均产生肠促胰岛素受体表达的显著增加。相比之下，在高血糖db/db胰岛中，AMPK抑制剂对肠促胰岛素受体表达的增强作用在低葡萄糖浓度下减弱。总之，AMPK参与在低葡萄糖浓度下胰岛中肠促胰岛素受体表达的调节。
The precise role of AMP-activated protein kinase (AMPK), a target of metformin, in pancreatic β cells remains controversial, even though metformin was recently shown to enhance the expression of incretin receptors (GLP-1 and GIP receptors) in pancreatic β cells. In this study, we investigated the effect of AMPK in the regulation of incretin receptors expression in pancreatic islets. The phosphorylation of AMPK in the mouse islets was decreased by increasing glucose concentrations. We showed the expression of incretin receptors in bell-shaped response to glucose; Expression of the incretin receptors in the isolated islets showed higher levels under a medium glucose concentration (11.1 mM) than that under a low glucose concentration (2.8 mM), but was suppressed under a high glucose concentration (22.2 mM). Both treatment with an AMPK inhibitor and DN-AMPK expression produced a significant increase of the incretin receptors expression under a low glucose concentration. By contrast, in hyperglycemic db/db islets, the enhancing effect of the AMPK inhibitor on the expression of incretin receptors was diminished under a low glucose concentration. Taken together, AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration.
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