Department of Endocrinology and Metabolism, Yokohama-City University, Yokohama, Japan.
PLoS One. 2013 May 22;8(5):e64633. doi: 10.1371/journal.pone.0064633. Print 2013.
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.
二甲双胍的作用靶点 AMP 激活蛋白激酶（AMPK）在胰腺β细胞中的确切作用仍存在争议，尽管最近的研究表明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。在这项研究中，我们研究了 AMPK 在调节胰腺胰岛中肠促胰岛素受体表达中的作用。葡萄糖浓度增加可降低小鼠胰岛中 AMPK 的磷酸化。我们发现肠促胰岛素受体的表达呈钟形响应葡萄糖。在分离的胰岛中，肠促胰岛素受体的表达在中等葡萄糖浓度（11.1mM）下高于低葡萄糖浓度（2.8mM），但在高葡萄糖浓度（22.2mM）下受到抑制。在低葡萄糖浓度下，用 AMPK 抑制剂处理和 DN-AMPK 表达均可显著增加肠促胰岛素受体的表达。相比之下，在高血糖 db/db 胰岛中，在低葡萄糖浓度下，AMPK 抑制剂对肠促胰岛素受体表达的增强作用减弱。总之，AMPK 参与了胰腺胰岛在低葡萄糖浓度下肠促胰岛素受体表达的调节。
