Yang Bao Chen, Wu Shang Ying, Leung Po Sing
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Ann Transl Med. 2020 Mar;8(6):310. doi: 10.21037/atm.2020.02.129.
Disruption of β-cell insulin secretion and viability caused by excessive ethanol consumption increases type 2 diabetes mellitus (T2DM) pathogenesis risk. Fibroblast growth factor 21 (FGF21) plays a significant role in regulating lipid and glucose homeostasis. Recently, FGF21, best known for its role in lipid and glucose homeostasis regulation, and its obligate co-receptor β-klotho have been shown to inhibit ethanol ingestion and metabolism. It remains unclear whether heavy ethanol intake modulates islet FGF21 expression and function. This study investigated the relationship between ethanol exposure, FGF21, and islet function / islet and cell models.
Mice were gavaged with 3.5 g/kg ethanol or saline for 1-3 weeks (long-term exposure). Human MIN6 cells and isolated islets were cultured and treated with 80 mM ethanol for 24 h (short-term exposure) to mimic excessive ethanol consumption. We applied the oral glucose tolerance test (OGTT), blood glucometry, enzyme-linked immunosorbent assay (ELISAs) for insulin and FGF21, glucose stimulated insulin secretion (GSIS) testing, reverse-transcription (RT)-polymerase chain reaction (PCR), and western blot experiments.
Long-term ethanol treatment induced FGF21 resistance in mouse pancreatic islets. Moreover, ethanol exposure damaged insulin secretory ability and glucose homeostasis. and experiments showed that short-term ethanol treatment upregulated the expression of FGF21 signaling pathway-related genes and proteins, without affecting β-cell survival or function.
Long-term ethanol consumption induces FGF21 resistance-mediated pancreatic β-cell dysfunction, and thus diabetes pathogenesis risk.
过量饮酒导致的β细胞胰岛素分泌和活力破坏会增加2型糖尿病（T2DM）发病风险。成纤维细胞生长因子21（FGF21）在调节脂质和葡萄糖体内平衡中起重要作用。最近，以其在脂质和葡萄糖体内平衡调节中的作用而闻名的FGF21及其必需的共受体β-klotho已被证明可抑制乙醇摄入和代谢。尚不清楚大量乙醇摄入是否会调节胰岛FGF21的表达和功能。本研究调查了乙醇暴露、FGF21与胰岛功能/胰岛及细胞模型之间的关系。
给小鼠灌胃3.5 g/kg乙醇或生理盐水，持续1 - 3周（长期暴露）。培养人MIN6细胞和分离的胰岛，并用80 mM乙醇处理24小时（短期暴露），以模拟过量饮酒。我们应用了口服葡萄糖耐量试验（OGTT）、血糖测定、胰岛素和FGF21的酶联免疫吸附测定（ELISA）、葡萄糖刺激胰岛素分泌（GSIS）测试、逆转录（RT）-聚合酶链反应（PCR）和蛋白质免疫印迹实验。
长期乙醇处理诱导小鼠胰岛产生FGF21抵抗。此外，乙醇暴露损害了胰岛素分泌能力和葡萄糖体内平衡。和实验表明，短期乙醇处理上调了FGF21信号通路相关基因和蛋白质的表达，而不影响β细胞存活或功能。
长期饮酒会诱导FGF21抵抗介导的胰腺β细胞功能障碍，从而增加糖尿病发病风险。
