Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Alcohol. 2012 Feb;46(1):89-99. doi: 10.1016/j.alcohol.2011.04.001. Epub 2011 Aug 12.
Chronic ethanol consumption increases the risk of type 2 diabetes mellitus, and ethanol has been reported to cause insulin resistance and, inconsistently, to reduce insulin secretion. The mechanism(s) underlying the reduction of insulin secretion by ethanol is not known. We used β-cell lines and isolated murine islets to determine the effect of ethanol on insulin content and secretion at low- and high-glucose concentrations, in the presence of KCl, diazoxide, tolbutamide, and regulators of cyclic AMP and protein kinase C (PKC). We also determined the gene expression of insulin; pancreas duodenum homeobox 1; and endoplasmic reticulum (ER) stress markers, such as Chop, ERp57, glucose-regulated protein 78/binding immunoglobulin protein, and inositol 1,4,5-triphosphate receptors. Ethanol reduced insulin secretion by interfering with muscarinic signaling and PKC activation but not the K-ATP channels. In addition, ethanol reduced insulin content and caused ER stress. The deleterious effects of ethanol on β-cells were prevented by 4-methyl pyrazole, an inhibitor of alcohol dehydrogenase, suggesting that ethanol metabolism is required for these effects.
慢性乙醇摄入会增加 2 型糖尿病的风险，有报道称乙醇可导致胰岛素抵抗，且不一致的是，还可减少胰岛素分泌。乙醇减少胰岛素分泌的机制尚不清楚。我们使用β细胞系和分离的鼠胰岛来确定在低钾、二氮嗪、甲苯磺丁脲和环 AMP 和蛋白激酶 C（PKC）调节剂存在的情况下，乙醇对低葡萄糖和高葡萄糖浓度下胰岛素含量和分泌的影响。我们还测定了胰岛素、胰腺十二指肠同源盒 1 和内质网（ER）应激标志物（如 Chop、ERp57、葡萄糖调节蛋白 78/结合免疫球蛋白蛋白和肌醇 1,4,5-三磷酸受体）的基因表达。乙醇通过干扰毒蕈碱信号和 PKC 激活来减少胰岛素分泌，但不影响 K-ATP 通道。此外，乙醇还降低了胰岛素含量并引起 ER 应激。乙醇脱氢酶抑制剂 4-甲基吡唑可预防这些对β细胞的有害作用，这表明这些作用需要乙醇代谢。
