Metformin stimulates FGF21 expression in primary hepatocytes.

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-10-15 DOI:10.1155/2012/465282
Eva B Nygaard, Sara G Vienberg, Cathrine Ørskov, Harald S Hansen, Birgitte Andersen
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引用次数: 55

Abstract

Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator of glucose and lipid metabolism; however, the exact mechanism of action and regulation of FGF21 is not fully understood. Metabolic status plays an important role in the regulation of FGF21, and we therefore examined whether metformin, an indirect AMPK-activator, regulates FGF21 expression in hepatocytes. FGF21 mRNA and protein expression were determined after incubation of primary cultured rat and human hepatocytes with metformin for 24 hours. To study the role of AMPK in the putative regulation of FGF21, hepatocytes were incubated with Compound C (an AMPK inhibitor) in the presence of metformin. A strong dose-dependent increase in FGF21 expression was observed in both rat and human hepatocytes treated with metformin. This effect was blocked by addition of the AMPK-inhibitor Compound C. The study shows that metformin is a potent inducer of hepatic FGF21 expression and that the effect of metformin seems to be mediated through AMPK activation. As FGF21 therapy normalizes blood glucose in animal models of type 2 diabetes, the induction of hepatic FGF21 by metformin might play an important role in metformin's antidiabetic effect.

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Abstract Image

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二甲双胍刺激原代肝细胞FGF21的表达。
成纤维细胞生长因子21 (FGF21)是一种新型的糖脂代谢调节因子;然而,FGF21的确切作用机制和调控尚不完全清楚。代谢状态在FGF21的调控中起重要作用,因此我们研究了二甲双胍(一种间接ampk激活剂)是否调节肝细胞中FGF21的表达。二甲双胍对原代培养的大鼠和人肝细胞孵育24小时后,检测FGF21 mRNA和蛋白的表达。为了研究AMPK在FGF21的调节中的作用,在二甲双胍存在的情况下,用化合物C (AMPK抑制剂)培养肝细胞。在二甲双胍处理的大鼠和人肝细胞中观察到FGF21表达的强烈剂量依赖性增加。这种作用被添加AMPK抑制剂化合物c阻断。研究表明,二甲双胍是肝脏FGF21表达的有效诱导剂,二甲双胍的作用似乎是通过AMPK激活介导的。由于FGF21治疗可使2型糖尿病动物模型的血糖正常化,二甲双胍诱导肝脏FGF21可能在二甲双胍的降糖作用中发挥重要作用。
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来源期刊
Experimental Diabetes Research
Experimental Diabetes Research 医学-内分泌学与代谢
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3-8 weeks
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