The myokine meteorin-like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKα2.,The FEBS Journal

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The myokine meteorin-like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKα2.
The FEBS Journal ( IF 5.5 ) Pub Date : 2020-04-19 , DOI: 10.1111/febs.15301
Jung Ok Lee ₁ , Won Seok Byun ₁ , Min Ju Kang ₁ , Jeong Ah Han ₁ , Jiyoung Moon ₂ , Min-Jeong Shin ₂ , Ho Jun Lee ₃ , Ji Hyung Chung ₃ , Jin-Seok Lee ₄ , Chang-Gue Son ₄ , Kwon-Ho Song ₅ , Tae Woo Kim _{5,

6} , Eun-Soo Lee ₇ , Hong Min Kim ₇ , Choon Hee Chung ₇ , Kevin R W Ngoei ₈ , Naomi X Y Ling ₉ , Jonathan S Oakhill _{9,

10} , Sandra Galic ₈ , Lisa Murray-Segal ₈ , Bruce E Kemp _{8,

10} , Kyoung Min Kim ₁₁ , Soo Lim ₁₁ , Hyeon Soo Kim ₁

Affiliation

Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
Department of Public Health Sciences, Korea University, Seoul, Korea.
Department of Biotechnology, CHA University, Gyeonggi-do, Korea.
Liver and Immunology Research Center, Oriental Medical College of Daejeon University, Korea.
Department of Biomedical Science, College of Medicine, Korea University, Seoul, Korea.
Department of Biochemistry and Molecular Biology, College of Medicine, Korea University, Seoul, Korea.
Department of Internal Medicine, Yonsei University College of Medicine, Wonju, Korea.
Protein Chemistry and Metabolism, St Vincent's Institute of Medical Research, University of Melbourne, Fitzroy, Vic., Australia.
Metabolic Signaling Laboratory, St Vincent's Institute of Medical Research, University of Melbourne, Fitzroy, Vic., Australia.
Mary MacKillop Institute for Health Research, Australian Catholic University, Fitzroy, Vic., Australia.
Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam, Korea.

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.

中文翻译：

通过靶向AMPKα2，类肌动蛋白Meterin-like（metrnl）改善了骨骼肌细胞和小鼠的葡萄糖耐量。

Meteorin-like（metrnl）是最近发现的一种能影响葡萄糖代谢的脂肪肌动蛋白。但是，其潜在的作用机理尚未完全了解。我们在这里显示，在电脉冲刺激下，在运动的小鼠体内，metrnl的水平增加，在体内，这表明metrnl是在肌肉收缩过程中分泌的。此外，metrnl以AMPKα2依赖性方式通过骨骼肌细胞中的钙依赖性AMPKα2途径增加葡萄糖摄取，并增加GLUT4的转录阻遏物HDAC5的磷酸化。磷酸化的HDAC5与14-3-3蛋白相互作用并将其隔离在细胞质中，从而激活GLUT4转录。腹膜内注射重组metrnl可改善高脂饮食诱发的肥胖或2型糖尿病小鼠的葡萄糖耐量，但对AMPKβ1β2肌肉特异性无效小鼠则无改善。Metrnl可通过AMPKα2改善葡萄糖代谢，是治疗2型糖尿病等与葡萄糖有关的疾病的有希望的候选药物。

更新日期：2020-03-20

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