Exercise mitigates Dapagliflozin-induced skeletal muscle atrophy in STZ-induced diabetic rats

Diabetology & Metabolic Syndrome

Research

Xudong Yang¹  Liangzhi Zhang¹  Lifeng Wang¹  Hengjun Lin²  Helong Quan³  Xia Zhai⁴  Xiusheng Sheng⁴ 

[1] College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua, Zhejiang, China;Exercise and Metabolism Research Center, Zhejiang Normal University, Jinhua, Zhejiang, China;Department of Colorectal anal surgery, Jinhua people’s hospital, 267 Danxi East Road, 321007, Jinhua, Zhejiang, China;Exercise and Metabolism Research Center, Zhejiang Normal University, Jinhua, Zhejiang, China;School of Sports Science and Physical Education, Research Center of Sports and Health Science, Northeast Normal University, 5268 Renmin Street, 130024, Changchun, Jilin, China;Medical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, Jinhua, Zhejiang, China;

关键词: Dapagliflozin;    Exercise;    Type 2 diabetes;    SGLT2 inhibitors;    Skeletal muscle atrophy;    Protein metabolism;   

DOI  :  10.1186/s13098-023-01130-w

 received in 2023-05-17, accepted in 2023-07-01,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2i) are commonly used in the management of type 2 diabetes mellitus (T2DM) and have been found to worsen the reduction of skeletal muscle mass in individuals with T2DM. This study aims to examine the potential of exercise in mitigating the skeletal muscle atrophy induced by SGLT2i treatment.MethodsA rat model of T2DM (40 male Sprague-Dawley rats; T2DM induced by a combination of high-fat diet and streptozotocin) was used to examine the effects of six-week treatment with Dapagliflozin (DAPA, SGLT2i) in combination with either aerobic exercise (AE) or resistance training (RT) on skeletal muscle. T2DM-eligible rats were randomized into the T2DM control group (CON, n = 6), DAPA treatment group (DAPA, n = 6), DAPA combined with aerobic exercise intervention group (DAPA + AE, n = 6), and DAPA combined with resistance training intervention group (DAPA + RT, n = 6). To assess the morphological changes in skeletal muscle, myosin ATPase and HE staining were performed. mRNA expression levels of Atrogin-1, MuRF1, and Myostatin were determined using quantitative PCR. Furthermore, protein expression levels of AKT, p70S6K, mTOR, FoXO1/3A, NF-κB, and MuRF1 were examined through western blotting.ResultsBoth the administration of DAPA alone and the combined exercise intervention with DAPA resulted in significant reductions in blood glucose levels and body weight in rats. However, DAPA alone administration led to a decrease in skeletal muscle mass, whereas RT significantly increased skeletal muscle mass and muscle fiber cross-sectional area. The DAPA + RT group exhibited notable increases in both total protein levels and phosphorylation levels of AKT and p70S6K in skeletal muscle. Moreover, the DAPA, DAPA + AE, and DAPA + RT groups demonstrated downregulation of protein expression (FoXO1/3A) and mRNA levels (Atrogin-1, MuRF1, and Myostatin) associated with muscle atrophy.ConclusionsOur findings provide support for the notion that dapagliflozin may induce skeletal muscle atrophy through mechanisms unrelated to protein metabolism impairment in skeletal muscle, as it does not hinder protein metabolic pathways while reduces muscle atrophy-related genes. Additionally, our observations reveal that RT proves more effective than AE in enhancing skeletal muscle mass and muscle fiber cross-sectional area in rats with T2DM by stimulating protein anabolism within the skeletal muscle.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023. corrected publication 2023

【 图 表 】

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