Obesity and insulin resistance are frequently associated with type 2 diabetes (T2D). Evidence is now revealed that plasma free fatty acid (FFA) levels are often elevated in most T2D patients, and this can cause peripheral insulin resistance directly. As a result, these FFAs inhibit insulin-stimulated glucose uptake, thus contributing to the onset of insufficient energy within cells. Among various T2D-related complications, the continuously loss of muscle is one of the most important adverse effects. Blocked insulin signaling in skeletal muscle is manifested by decreased insulin sensitivity and impaired muscle cell function including glucose transport, glucose phosphorylation, reduced glucose oxidation and glycogen synthesis that might ultimately lead to muscle loss. Interestingly, recent studies have found that GLP-1 agonists appear to slow muscle wasting during T2D. Since GLP-1 receptors are abundantly expressed on the membrane of muscle cells, indicating that they may play some important roles in muscle physiology. However, the detailed mechanism is still not well understood. In this study, we investigated the effect of GLP-1 agonist against FFA-induced muscle wasting. We used mouse C2C12 myotubes to evaluate effects of GLP-1 agonists FFA-induced muscle loss and dysfunction. Our data indicated that FFA induces insulin resistance, oxidative stress muscle loss and cell senescence in muscle cells. Moreover, FFA also decreased glucose uptake and reduced myotube mass and function. Conversely, GLP-1 agonists could protect against FFAs-induced myotube dysfunctions, including insulin resistance, oxidative stress, cell loss and senescence, that eventually reversed myotube mass and function through AMPK/SIRT1 pathway. We expect our results can extend the contributing role of GLP-1 signaling in FFA-induced insulin resistance of muscle cells, and the modulation of GLP-1 signaling may be a workable strategy for muscle wasting prevention.
H. Li: None. C. Lin: None. C. Huang: None. E. Kornelius: None. Y. Yang: None. C. Peng: None. C. Li: None. S. Liu: None.
Ministry of Science and Technology of Taiwan (108-2320-B-040-029-MY2)