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.