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The myokine meteorin-like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKa2
Lee, Jung Ok Byun, Won Seok Kang, Min Ju Han, Jeong Ah Moon, Jiyoung Shin, Min-Jeong Lee, Ho Jun Chung, Ji Hyung Lee, Jin-Seok Son, Chang-Gue
Lee, Jung Ok
Byun, Won Seok
Kang, Min Ju
Han, Jeong Ah
Moon, Jiyoung
Shin, Min-Jeong
Lee, Ho Jun
Chung, Ji Hyung
Lee, Jin-Seok
Son, Chang-Gue
Author
Lee, Jung Ok
Byun, Won Seok
Kang, Min Ju
Han, Jeong Ah
Moon, Jiyoung
Shin, Min-Jeong
Lee, Ho Jun
Chung, Ji Hyung
Lee, Jin-Seok
Son, Chang-Gue
Song, Kwon-Ho
Kim, Tae Woo
Lee, Eun-Soo
Kim, Hong Min
Chung, Choon Hee
Ngoei, Kevin R. W.
Ling, Naomi X. Y.
Oakhill, Jonathan S.
Galic, Sandra
Murray-Segal, Lisa
Kemp, Bruce E.
Kim, Kyoung Min
Lim, Soo
Kim, Hyeon Soo
Byun, Won Seok
Kang, Min Ju
Han, Jeong Ah
Moon, Jiyoung
Shin, Min-Jeong
Lee, Ho Jun
Chung, Ji Hyung
Lee, Jin-Seok
Son, Chang-Gue
Song, Kwon-Ho
Kim, Tae Woo
Lee, Eun-Soo
Kim, Hong Min
Chung, Choon Hee
Ngoei, Kevin R. W.
Ling, Naomi X. Y.
Oakhill, Jonathan S.
Galic, Sandra
Murray-Segal, Lisa
Kemp, Bruce E.
Kim, Kyoung Min
Lim, Soo
Kim, Hyeon Soo
Abstract
Meteorin‐like (metrnl) is a recently identified adipomyokine that beneficially affects glucose metabolism; however, its underlying mechanism of action is not completely understood. We here show that the level of metrnl increases in vitro under electrical pulse stimulation and in vivo in exercised mice, suggesting that metrnl is secreted during muscle contractions. In addition, metrnl increases glucose uptake via the calcium‐dependent AMPKα2 pathway in skeletal muscle cells and increases the phosphorylation of HDAC5, a transcriptional repressor of GLUT4, in an AMPKα2‐dependent manner. Phosphorylated HDAC5 interacts with 14‐3‐3 proteins and sequesters them in the cytoplasm, resulting in the activation of GLUT4 transcription. An intraperitoneal injection of recombinant metrnl improved glucose tolerance in mice with high‐fat‐diet‐induced obesity or type 2 diabetes, but not in AMPK β1β2 muscle‐specific null mice. Metrnl improves glucose metabolism via AMPKα2 and is a promising therapeutic candidate for glucose‐related diseases such as type 2 diabetes.
Keywords
adipomyokine, AMPK, glucose uptake, Metrnl, type 2 diabetes
Date
2020
Type
Journal article
Journal
The FEBS Journal
Book
Volume
287
Issue
10
Page Range
2087-2104
Article Number
ACU Department
Non-faculty
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Published as ‘gold’ (paid) open access
License
CC BY 4.0
File Access
Open