标题：Ethanol induced impairment of glucose metabolism involves alterations of GABAergic signaling in pancreatic beta-cells
作者：Wang, Shuanglian; Luo, Yan; Feng, Allen; Li, Tao; Yang, Xupeng; Nofech-Mozes, Roy; Yu, Meng; Wang, Changhui; Li, Ziwei; Yi, Fan; L 更多 作者机构：[Wang, Shuanglian; Li, Tao; Yang, Xupeng; Yu, Meng; Wang, Changhui; Li, Ziwei; Liu, Chuanyong] Shandong Univ, Dept Physiol, Sch Med, Jinan 250100, Sha 更多
通讯作者地址：[Liu, CY]Shandong Univ, Dept Physiol, Sch Med, Jinan 250100, Shandong, Peoples R China.
关键词：Alcohol overindulgence; Pancreatic islet beta-cells; GABA receptor;; Insulin; Glucose metabolism
摘要：Alcohol overindulgence is a risk factor of type 2 diabetes mellitus. However, the mechanisms by which alcohol overindulgence damages glucose metabolism remain unclear. Pancreatic islet beta-cells are endowed with type-A gamma-aminobutyric acid receptor (GABA(A)R) mediated autocrine signaling mechanism, which regulates insulin secretion and fine-tunes glucose metabolism. In neurons GABA(A)R is one of the major targets for alcohol. This study investigated whether ethanol alters glucose metabolism by affecting GABA(A)R signaling in pancreatic beta-cells. Blood glucose level of test mice was measured using a blood glucose meter. Insulin secretion by the pancreatic beta-cell line INS-1 cells was examined using a specific insulin ELISA kit. Whole-cell patch-clamp recording was used to evaluate GABA-elicited current in INS-1 cells. Western blot and immunostaining were used to measure the expression of GABA(A)R subunits in mouse pancreatic tissues or in INS-1 cells. Intraperitoneal (i.p.) administration of ethanol (3.0 g/kg body weight) to mice altered glucose metabolism, which was associated with decreased expression of GABA(A)R alpha 1- and delta- subunits on the surface of pancreatic beta-cells. Acute treatment of cultured INS-lcells with ethanol (60 mM) decreased the GABA-induced current and reduced insulin secretion. In contrast, treating INS-1 cells with GABA (100 mu M) largely prevented the ethanol-induced reduction of insulin release. Importantly, pre-treating mice with GABA (i.p., 1.5 mg/kg body weight) partially reversed ethanol-induced impairment of glucose homeostasis in mice. Our data suggest a novel role of pancreatic GABA signaling in protecting pancreatic islet beta-cells from ethanol-induced dysfunction. (C) 2014 Elsevier Ireland Ltd. All rights reserved.