Exercise and Metabolism Research Center, College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua, Zhejiang, China.
Department of Colorectal anal Surgery, Jinhua People's Hospital, Jinhua, Zhejiang, China.
Biomed Pharmacother. 2023 Dec 31;169:115852. doi: 10.1016/j.biopha.2023.115852. Epub 2023 Nov 7.
Type 2 diabetes mellitus (T2DM) is a prevalent, chronic metabolic disease. Sodium-glucose cotransporter-2 (SGLT2) inhibitors and aerobic exercise (AE) have shown promise in mitigating insulin resistance (IR) and T2DM. This study investigated the effects of dapagliflozin (Dapa) monotherapy and combined AE on mitochondrial quality control (MQC) in skeletal muscle and IR in T2DM rats. T2DM rats, induced by a high-fat diet/streptozotocin model, were randomly assigned to the following groups: T2DM+vehicle group (DMV), T2DM rats treated with Dapa (DMDa, 10 mg/kg/d), T2DM rats subjected to combined Dapa treatment and AE (DMDa+AE), and the standard control group (CON). Blood and skeletal muscle samples were collected after 6 weeks of intragastric administration and treadmill exercise. The results showed that DMDa monotherapy could reduce the accumulation of white adipose tissue and skeletal muscle lipid droplets and improve HOMA-IR. While the combined AE led to further reductions in subcutaneous white adipose tissue and fasting glucose levels, it did not confer additional benefits in terms of HOMA-IR. Furthermore, Dapa monotherapy enhanced skeletal muscle mitochondrial biogenesis (PGC-1α, NRF1, TFAM, and COX IV), mitochondrial dynamics (OPA1, DRP1, and MFN2), and mitophagy (PGAM5 and PINK1) related protein levels. Nevertheless, the combination of Dapa with AE treatment did not yield an additive effect. In conclusion, this study highlights the potential of SGLT2 inhibitors, specifically Dapa, in ameliorating IR and maintaining MQC in skeletal muscle in rats with T2DM. However, combined AE did not produce an additive effect, indicating the need for further research.
2 型糖尿病（T2DM）是一种常见的慢性代谢性疾病。钠-葡萄糖共转运蛋白-2（SGLT2）抑制剂和有氧运动（AE）已被证明可改善胰岛素抵抗（IR）和 T2DM。本研究探讨了达格列净（Dapa）单药治疗和联合 AE 对骨骼肌线粒体质量控制（MQC）和 T2DM 大鼠 IR 的影响。通过高脂肪饮食/链脲佐菌素模型诱导 T2DM 大鼠，将其随机分为以下几组：T2DM+vehicle 组（DMV）、T2DM 大鼠用 Dapa 治疗（DMDa，10mg/kg/d）、T2DM 大鼠联合 Dapa 治疗和 AE（DMDa+AE）和标准对照组（CON）。灌胃 6 周后和跑步机运动后采集血液和骨骼肌样本。结果表明，DMDa 单药治疗可减少白色脂肪组织和骨骼肌脂质滴的积累，改善 HOMA-IR。而联合 AE 导致皮下白色脂肪组织和空腹血糖水平进一步降低，但在 HOMA-IR 方面没有额外获益。此外，Dapa 单药治疗可增强骨骼肌线粒体生物发生（PGC-1α、NRF1、TFAM 和 COX IV）、线粒体动力学（OPA1、DRP1 和 MFN2）和线粒体自噬（PGAM5 和 PINK1）相关蛋白水平。然而，Dapa 与 AE 联合治疗并没有产生附加效应。总之，本研究强调了 SGLT2 抑制剂，特别是 Dapa，在改善 T2DM 大鼠 IR 和维持骨骼肌 MQC 方面的潜力。然而，联合 AE 没有产生附加效应，表明需要进一步研究。
