Irisin, a Novel Myokine, Regulates Glucose Uptake in Skeletal Muscle Cells via AMPK

Abstract

Irisin is a novel myokine produced by skeletal muscle. However, its metabolic role is poorly understood. In the present study, irisin induced glucose uptake in differentiated skeletal muscle cells. It increased AMP-activated protein kinase (AMPK) phosphorylation and the inhibition of AMPK blocked glucose uptake. It also increased reactive oxygen species (ROS) generation. N-acetyl cysteine, a ROS scavenger, blocked irisin-induced AMPK phosphorylation. Moreover, irisin activated p38 MAPK in an AMPK-dependent manner. The inhibition and knockdown of p38 MAPK blocked irisin-induced glucose uptake. A colorimetric absorbance assay showed that irisin stimulated the translocation of glucose transporter type 4 to the plasma membrane and that this effect was suppressed in cells pretreated with a p38 MAPK inhibitor or p38 MAPK small interfering RNA. In primary cultured myoblast cells, irisin increased the concentration of intracellular calcium. STO-609, a calcium/calmodulin-dependent protein kinase kinase inhibitor, blocked irisin-induced AMPK phosphorylation, implying that calcium is involved in irisin-mediated signaling. Our results suggest that irisin plays an important role in glucose metabolism via the ROS-mediated AMPK pathway in skeletal muscle cells.

Serum irisin and its regulation by hyperinsulinemia in women with polycystic ovary syndrome

“…Moreover, irisin has been shown to induce glucose uptake in differentiated skeletal muscle cells by stimulating the translocation of GLUT4 to the plasma membrane [5]. Elevated serum irisin concentration has been found to be related to an increase in energy expenditure, weight loss and improved diet-induced insulin resistance in mice [1].…”

Can irisin be a linker between physical activity and brain function?

“…Studies on the intracellular signaling pathway activated by irisin also suggest the presence of a functional receptor for this molecule in a variety of cells. In the skeletal muscle, irisin has been reported to activate the AMP-activated protein kinase (AMPK)-p38 MAPK signaling (32). Our studies reveal the AMPK-SREBP2 signaling pathway activated by irisin in hepatocytes (33).…”

Physical Exercise Induces Irisin Levels Associated With Improved Cognitive Functions and Glucose Tolerance in Obese and Normal Weight Egyptian Subjects: A 3-Month Interventional Study.

“…Partial support of this role of irisin come from experimental animal models, in which systemic irisin administration was found to improve insulin resistance and enhances lipolysis in obese rats. 46,47 One limitation of our study is that it could only provide a proof of association, and not causation, between exerciseinduced irisin levels and the observed improved cognitive and glucose tolerance parameters. Although the reported correlations in our study were adjusted by controlling for many confounding and potentially explanatory variables, yet physical exercise could improve cognitive performance and glucose regulation by other mechanisms.…”