Chronically elevated fatty acids, especially saturated fatty acids can cause the body to be unresponsive to insulin and in turn reduces insulin-stimulated glucose uptake (insulin resistance). However, actually, plasma fatty acid concentrations vary widely from hour to hour and display waves according to nutritional state and the presence of regulators including hormones, as well as metabolic and neural signals. The acute effect of fatty acids to the main energy consumer, skeletal muscle tissue is inconsistent and the underlying molecular mechanisms are still unclear. A recent study demonstrated how fatty acid influences the glucose uptake acutely and revealed the involved molecular mechanism. This study was conducted by Professor Pingsheng Liu and his colleagues at the Institute of Biophysics, Chinese Academy of Sciences.

In their study, Professor Liu’s group found that palmitic acid can acutely stimulated glucose uptake by the binding of palmitic acid to cell surface and followed by PI3K/AMPK/Akt and PI3K/ERK1/2 pathways independently. They showed that palmitic acid rapidly induces GLUT4 translocation and stimulates glucose uptake as fast as 5-minute treatment in rat skeletal muscle cell line L6. Phosphorylation of AMP-activated protein kinase (AMPK), Akt and extracellular signal-related kinase1/2 (ERK1/2) is enhanced by palmitic acid in a time-dependent manner, and inhibiting their activities can decrease the glucose uptake. PI3K inhibitor decreases AMPK, Akt and ERK1/2 phosphorylation as well as palmitic acid-induced glucose uptake. In addition, weakening AMPK activity reduces phosphorylation of Akt but not ERK1/2, and Akt inhibitor can not affect ERK1/2 activation either. Meanwhile, ERK1/2 inhibitors have no effect on Akt phosphorylation.

This study not only provides us a new picture of fatty acid effects on glucose uptake in skeletal muscle cells but also offers a different view for understanding the pathology of type 2 diabetes.

Fig. In response to plasma membrane-bound palmitate, signal is transduced by activation of PI3K/AMPK/Akt and PI3K/ERK1/2, which in turn leads GLUT4 translocation to plasma membrane and glucose uptake in skeletal muscle cells. (by Jing Pu, et al)

This work was published on line as an original research article in Journal of Lipid Research.