Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway
Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway
复制标题
鸢尾素通过调节 AMPK 信号通路改善 2 型糖尿病的脂肪酸氧化和葡萄糖利用
DOI：
10.1038/ijo.2015.199
复制
发表时间：
2016-03-01
影响因子：
4.9
通讯作者：
Tao, L.
中科院分区：
文献类型：
--
作者：
Xin, C.;Liu, J.;Tao, L.
方法：采用高脂饲料喂养C57BL/6小鼠，建立小鼠糖尿病模型。然后用鸢尾素治疗糖尿病小鼠。为了模拟体外2型糖尿病，肌细胞和肝细胞在高糖高脂培养基中培养。观察葡萄糖摄取、脂肪酸氧化及相关蛋白的表达。结果：鸢尾素改善葡萄糖耐量和葡萄糖摄取，糖尿病骨骼肌中18 F-FDG积累和GLUT4易位增加。鸢尾素也增加了在高葡萄糖/高脂肪酸培养基中培养的肌细胞的葡萄糖摄取。相反，鸢尾素降低了糖尿病肝脏中参与糖异生的PEPCK和G6Pase的表达。鸢尾素一贯降低糖尿病小鼠的脂肪重量和血清总胆固醇和甘油三酯水平，但增加肌肉组织中乙酰辅酶A羧化酶-β磷酸化和脂肪组织中解偶联蛋白1的表达。此外，鸢尾素增加了肌细胞中脂肪酸的氧化。抑制单磷酸腺苷（AMP）激活的蛋白激酶（AMPK）可减弱鸢尾素对肌细胞中葡萄糖摄取和脂肪酸β-氧化的影响。同样，通过特定抑制剂抑制AMPK可以降低鸢尾素对肝细胞中PEPCK和G6Pase表达的影响。结论：鸢尾素在葡萄糖利用和脂质代谢中具有重要作用，鸢尾素是治疗糖尿病及其并发症的有前景的药理靶点。
Methods:A mouse model of diabetes was established by feeding C57BL/6 mice with high-fat diet. The diabetic mice were then treated with irisin. To mimic type 2 diabetes in vitro, myocytes and hepatocytes were cultured in a medium of high glucose and high fat. Glucose uptake, fatty acid oxidation and the expression of related protein were evaluated.Results:Irisin improved glucose tolerance and glucose uptake as evidenced by increased 18 F-FDG accumulation and GLUT4 translocation in diabetic skeletal muscle. Irisin also increased glucose uptake in myocytes cultured in high glucose/high fatty acid medium. In contrast, irisin reduced the expression of PEPCK and G6Pase, which are involved in gluconeogenesis, in diabetic liver. Consistently, irisin reduced fat weight and serum total cholesterol and triglyceride levels in diabetic mice, but increased acetyl coenzyme A carboxylase-β phosphorylation in muscle tissue and uncoupling protein 1 expression in fat tissue. In addition, irisin increased the oxidation of fatty acid in myocytes. Knockdown of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) attenuated the effects of irisin on glucose uptake and fatty acid β-oxidation in myocytes. Similarly, inhibition of AMPK by a specific inhibitor reduced the effects of irisin on PEPCK and G6Pase expression in hepatocytes.Conclusions:Our results suggest that irisin has an essential role in glucose utilization and lipid metabolism, and irisin is a promising pharmacological target for the treatment of diabetes and its complications.