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

作者：Xudong Yang, Lifeng Wang, Liangzhi Zhang, Xia Zhai, Xiusheng Sheng, Helong Quan, Hengjun Lin · 发表于：Diabetology & Metabolic Syndrome · 年份：2023 · DOI：10.1186/s13098-023-01130-w · 被引用次数：17 · 研究领域：Muscle Physiology and Disorders、Metabolism, Diabetes, and Cancer、Adipose Tissue and Metabolism

BACKGROUND: Sodium-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. METHODS: A 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. RESULTS: Both 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 ske...