Neuregulins increase mitochondrial oxidative capacity and insulin sensitivity in skeletal muscle cells
Neuregulins increase mitochondrial oxidative capacity and insulin sensitivity in skeletal muscle cells
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DOI：
10.2337/db06-1726
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发表时间：
2007-09-01
期刊：
影响因子：
7.7
通讯作者：
Guma, Anna
中科院分区：
文献类型：
--
作者：
Canto, Carles;Pich, Sara;Guma, Anna
神经调节蛋白是对肌肉发生和调节肌肉代谢至关重要的生长因子。向发育中的L 6 E9肌细胞添加含有3 nmol/l生物活性表皮生长因子样结构域的重组神经调节蛋白-1同种型heregulin-β 1（177-244）（Hrg）对葡萄糖摄取具有急性和慢性作用并增强肌生成。在这里，我们研究了代谢适应的肌细胞慢性治疗Hrg.RESEARCH设计和方法-L 6 E9和C2 C12肌细胞进行了慢性治疗低浓度的Hrg（3 pmol/l），不诱导肌生成。我们分析了Hrg对细胞氧化代谢和胰岛素敏感性的影响，并探讨了其作用机制。葡萄糖和棕榈酸的氧化增加，而乳酸的释放减少。Hrg增加氧化磷酸化（OXPHOS）亚基的丰度，增强线粒体膜电位，并诱导过氧化物酶体增殖物激活受体（PPAR）γ共激活因子1 α和PPAR δ的表达。此外，我们确定了过氧化物酶体增殖物激活受体δ作为一个重要的调解人的刺激作用的Hrg的表达OXPHOS亚基。神经调节蛋白治疗后L 6 E9肌管的较高的氧化能力也增加了胰岛素敏感性和胰岛素信号potential.CONCLUSIONS-These结果表明，神经调节蛋白作为氧化能力和胰岛素敏感性在肌肉细胞中的关键调制器。
OBJECTIVE-Neuregulins are growth factors that are essential for myogenesis and regulate muscle metabolism. The addition of a recombinant neuregulin-1 isoform, heregulin-beta 1(177-244) (Hrg), containing 3 nmol/l of the bioactive epidermal growth factor-like domain, to developing L6E9 myocytes has acute and chronic effects on glucose uptake and enhances myogenesis. Here, we studied the metabolic adaptation of myocytes to chronic treatments with Hrg.RESEARCH DESIGN AND METHODS-L6E9 and C2C12 myocytes were chronically treated with low concentrations of Hrg (3 pmol/l) that do not induce myogenesis. We analyzed the effects of Hrg on cellular oxidative metabolism and insulin sensitivity and explored the mechanisms of action.RESULTS-Hrg increased the cell content of GLUT4 without affecting basal glucose uptake. Glucose and palmitate oxidation increased in Hrg-treated cells, whereas lactate release decreased. Hrg increased the abundance of oxidative phosphorylation (OXPHOS) subunits, enhanced mitochondrial membrane potential, and induced the expression of peroxisome proliferator-activated receptor (PPAR)gamma coactivator1 alpha and PPAR delta. Furthermore, we identified PPAR delta as an essential mediator of the stimulatory effects of Hrg on the expression of OXPHOS subunits. The higher oxidative capacity of L6E9 myotubes after neuregulin treatment also paralleled an increase in insulin sensitivity and insulin signaling potency.CONCLUSIONS-These results indicate that neuregulins act as key modulators of oxidative capacity and insulin sensitivity in muscle cells.