Fatty acid-binding protein 3 stimulates glucose uptake by facilitating AS160 phosphorylation in mouse muscle cells
Fatty acid-binding protein 3 stimulates glucose uptake by facilitating AS160 phosphorylation in mouse muscle cells
复制标题
DOI：
10.1111/j.1365-2443.2011.01517.x
复制
发表时间：
2011-06-01
期刊：
影响因子：
2.1
通讯作者：
Yamashita, Hitoshi
中科院分区：
文献类型：
--
作者：
Kusudo, Tatsuya;Kontani, Yasuhide;Yamashita, Hitoshi
我们在体内研究了脂肪酸结合蛋白3（FABP3）与肥胖之间的关系，以及体外FABP3对骨骼肌细胞葡萄糖摄取信号转导的影响。在肥胖小鼠中，腓肠肌中的 FABP3 蛋白水平随着体重和代谢表型的增加而显着增加，表明肌肉中 FABP3 的表达与小鼠肥胖和/或胰岛素抵抗的发展之间存在密切关系。在使用编码人 FABP3 的腺病毒感染的 C2C12 肌管进行的实验中，诱导刺激了葡萄糖摄取，而无需胰岛素刺激，同时 AMP 激活蛋白激酶 (AMPK) 和 AS160 的磷酸化增加。与对照细胞相比，FABP3 诱导的肌管中胰岛素以加性方式增强葡萄糖摄取，同时增加 Akt 和 AS160 的磷酸化。即使在棕榈酸酯存在的情况下，在胰岛素刺激下 FABP3 诱导的肌管中葡萄糖摄取也会增加，与对照组相比，检测到的 Akt 磷酸化显着升高。这些结果表明 FABP3 通过促进骨骼肌中 AMPK 依赖性 AS160 磷酸化来刺激葡萄糖摄取。 FABP3 还可能通过在脂毒性条件下维持细胞中胰岛素依赖性 Akt 激活来促进 AS160 磷酸化。
We studied the relationship between fatty acid-binding protein 3 (FABP3) and obesity in vivo and the effects of FABP3 on signal transduction for glucose uptake in skeletal muscle cells in vitro. In obese mice, the level of FABP3 protein in gastrocnemius muscles increased significantly with an increase in body weight and metabolic phenotypes, suggesting a close relationship between FABP3 expression in the muscle and the development of obesity and/or insulin resistance in mice. In experiments using C2C12 myotubes infected with adenoviruses encoding human FABP3, induction stimulated glucose uptake without insulin stimulation in parallel with increases in the phosphorylation of AMP-activated protein kinase (AMPK) and AS160. Insulin enhanced glucose uptake in an additive fashion with increased phosphorylation of Akt and AS160 in FABP3-induced myotubes compared to control cells. This increased glucose uptake in FABP3-induced myotubes with insulin stimulation was found even in the presence of palmitate, in which a significantly higher Akt phosphorylation was detected compared to controls. These results suggest that FABP3 stimulates glucose uptake by facilitating AMPK-dependent AS160 phosphorylation in skeletal muscle. FABP3 may also contribute to AS160 phosphorylation by maintaining insulin-dependent Akt activation in the cells under a lipotoxic condition.