Effects of dapagliflozin monotherapy and combined aerobic exercise on skeletal muscle mitochondrial quality control and insulin resistance in type 2 diabetes mellitus rats
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 combin...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223016505 |
| _version_ | 1797404576323731456 |
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| author | Liangzhi Zhang Hengjun Lin Xudong Yang Jipeng Shi Xiusheng Sheng Lifeng Wang Ting Li Helong Quan Xia Zhai Wei Li |
| author_facet | Liangzhi Zhang Hengjun Lin Xudong Yang Jipeng Shi Xiusheng Sheng Lifeng Wang Ting Li Helong Quan Xia Zhai Wei Li |
| author_sort | Liangzhi Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T02:57:00Z |
| format | Article |
| id | doaj.art-66ca00b023064854b7a464f6fef02dcf |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-09T02:57:00Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-66ca00b023064854b7a464f6fef02dcf2023-12-05T04:14:32ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01169115852Effects of dapagliflozin monotherapy and combined aerobic exercise on skeletal muscle mitochondrial quality control and insulin resistance in type 2 diabetes mellitus ratsLiangzhi Zhang0Hengjun Lin1Xudong Yang2Jipeng Shi3Xiusheng Sheng4Lifeng Wang5Ting Li6Helong Quan7Xia Zhai8Wei Li9Exercise and Metabolism Research Center, College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua, Zhejiang, ChinaDepartment of Colorectal anal Surgery, Jinhua People's Hospital, Jinhua, Zhejiang, ChinaExercise and Metabolism Research Center, College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua, Zhejiang, ChinaExercise Capacity Assessment and Promotion Research Center, School of Physical Education, Northeast Normal University, Changchun, Jilin, ChinaMedical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, Jinhua, Zhejiang, ChinaExercise and Metabolism Research Center, College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua, Zhejiang, ChinaExercise and Metabolism Research Center, College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua, Zhejiang, ChinaExercise Capacity Assessment and Promotion Research Center, School of Physical Education, Northeast Normal University, Changchun, Jilin, China; Correspondence to: Exercise Capacity Assessment and Promotion Research Center, School of Physical Education, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin 130024, China.Medical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, Jinhua, Zhejiang, China; Correspondence to: Medical Molecular Biology Laboratory, School of Medicine, Jinhua Polytechnic, 1188 Wuzhou Road, Jinhua, Zhejiang 321007, China.Exercise and Metabolism Research Center, College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua, Zhejiang, China; Correspondence to: Exercise and Metabolism Research Center, College of Physical Education and Health Sciences, Zhejiang Normal University, 688 Yingbin Avenue, Jinhua, Zhejiang 321004, China.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.http://www.sciencedirect.com/science/article/pii/S0753332223016505DapagliflozinAerobic exerciseType 2 diabetes mellitusInsulin resistanceSkeletal muscleMitochondrial quality control |
| spellingShingle | Liangzhi Zhang Hengjun Lin Xudong Yang Jipeng Shi Xiusheng Sheng Lifeng Wang Ting Li Helong Quan Xia Zhai Wei Li Effects of dapagliflozin monotherapy and combined aerobic exercise on skeletal muscle mitochondrial quality control and insulin resistance in type 2 diabetes mellitus rats Biomedicine & Pharmacotherapy Dapagliflozin Aerobic exercise Type 2 diabetes mellitus Insulin resistance Skeletal muscle Mitochondrial quality control |
| title | Effects of dapagliflozin monotherapy and combined aerobic exercise on skeletal muscle mitochondrial quality control and insulin resistance in type 2 diabetes mellitus rats |
| title_full | Effects of dapagliflozin monotherapy and combined aerobic exercise on skeletal muscle mitochondrial quality control and insulin resistance in type 2 diabetes mellitus rats |
| title_fullStr | Effects of dapagliflozin monotherapy and combined aerobic exercise on skeletal muscle mitochondrial quality control and insulin resistance in type 2 diabetes mellitus rats |
| title_full_unstemmed | Effects of dapagliflozin monotherapy and combined aerobic exercise on skeletal muscle mitochondrial quality control and insulin resistance in type 2 diabetes mellitus rats |
| title_short | Effects of dapagliflozin monotherapy and combined aerobic exercise on skeletal muscle mitochondrial quality control and insulin resistance in type 2 diabetes mellitus rats |
| title_sort | effects of dapagliflozin monotherapy and combined aerobic exercise on skeletal muscle mitochondrial quality control and insulin resistance in type 2 diabetes mellitus rats |
| topic | Dapagliflozin Aerobic exercise Type 2 diabetes mellitus Insulin resistance Skeletal muscle Mitochondrial quality control |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223016505 |
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