Meteorin like (Metrnl) adipomyokine improves glucose tolerance in type 2 diabetes via AMPK pathway
Meteorin like (metrnl) is a recently identified adipomyokine that has beneficial effects on glucose metabolism. However, its underlying mechanism of action is not completely understood. In this study, we have shown that a level of metrnl increase in vitro under electrical pulse stimulation (EPS) and in vivo in exercise mice, suggesting that metrnl is an exercise induced myokine. In addition, metrnl increases glucose uptake through the calcium dependent AMPK pathway. Metrnl also increases the phosphorylation of HDAC5, a transcriptional repressor of GLUT4, in an AMPK dependent manner. Phosphorylated HDAC5 interacts with 14 3 3 proteins and sequesters them in the cytoplasm, resulting in the activation of GLUT4 transcription. The intraperitoneal injection of recombinant metrnl improves glucose tolerance in mice with high fat induced obesity or type 2 diabetes (db/db) but this is not seen in AMPK b1b2 muscle specific null mice (AMPK b1b2 MKO) In conclusion, we have demonstrated that metrnl induces beneficial effects on glucose metabolism via AMPK and is a promising therapeutic candidate for glucose related diseases such as type 2 diabetes.