PT  - JOURNAL ARTICLE
AU  - Jung Ok Lee
AU  - Hye Jeong Lee
AU  - Yong Woo Lee
AU  - Jeong Ah Han
AU  - Min Ju Kang
AU  - Jiyoung Moon
AU  - Min-Jeong Shin
AU  - Ho Jun Lee
AU  - Ji Hyung Chung
AU  - Jin-Seok Lee
AU  - Chang-Gue Son
AU  - Kwon-Ho Song
AU  - Tae Woo Kim
AU  - Eun-Soo Lee
AU  - Hong min Kim
AU  - Choon Hee Chung
AU  - Kevin R.W. Ngoei
AU  - Naomi X.Y. Ling
AU  - Jonathan S. Oakhill
AU  - Sandra Galic
AU  - Lisa Murray-Segal
AU  - Bruce E. Kemp
AU  - Kyoung Min Kim
AU  - Soo Lim
AU  - Hyeon Soo Kim
TI  - Meteorin-like (Metrnl) adipomyokine improves glucose tolerance in type 2 diabetes via AMPK pathway
AID  - 10.1101/420489
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 420489
4099  - http://biorxiv.org/content/early/2018/09/18/420489.short
4100  - http://biorxiv.org/content/early/2018/09/18/420489.full
AB  - 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 β1β2 muscle-specific null mice (AMPK β1β2 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.