高强度间歇训练与限时进食对2型糖尿病大鼠肌肉组织中AKT-IGF-1-mTOR信号通路的联合作用

The Combined Effect of High-Intensity Interval Training and Time-Restricted Feeding on the AKT-IGF-1-mTOR Signaling Pathway in the Muscle Tissue of Type 2 Diabetic Rats.

作者信息

Mohebinejad Motahareh, Kazeminasab Fatemeh, Ghanbari Rad Mahtab, Bagheri Reza, Razi Mazdak, Willoughby Darryn, Dutheil Fred

机构信息

Department of Physical Education and Sports Science, Faculty of Humanities, University of Kashan, Kashan 87317-53153, Iran.

Gerash Cellular and Molecular Research Center, Gerash University of Medical Sciences, Gerash 58666-74417, Iran.

出版信息

Nutrients. 2025 Apr 22;17(9):1404. doi: 10.3390/nu17091404.

Abstract

High-intensity interval training (HIIT) and time-restricted feeding (TRF) have shown potential in enhancing glucose metabolism, increasing insulin sensitivity, and promoting muscle health. This study investigates the combined effects of HIIT and TRF on the AKT-IGF-1-mTOR signaling pathway in the muscle tissue of type 2 diabetic (T2D) rats. 42 male Wistar rats (4-5 weeks of age) were included in the study. The animals were randomly divided into two groups: 1. Standard diet (SD) non-diabetic ( = 7) and 2. High-fat diet (HFD = 35) for 4 weeks. T2D was induced by intraperitoneal injection (IP) of streptozotocin (STZ) at 35 mg/kg. Animals with blood glucose levels ≥ 250 mg/dL were considered diabetic. Diabetic rats were randomly divided into five groups ( = 7): 1. Diabetes-HIIT (D-HIIT), 2. Diabetes-TRF (D-T), 3. Diabetes-combined TRF and HIIT (D-T+HIIT), 4. Diabetes-Untreated Control (D), and 5. Diabetes with metformin (D-MET). The HIIT protocol and TRF regimen were followed for 10 weeks. Muscle tissue was collected for histological analysis, and the expression of proteins related to the AKT-IGF-1-mTOR pathway was measured. Blood glucose levels, insulin resistance (IR), and markers of muscle degradation were significantly improved in the D-T+HIIT and D-MET groups compared to the non-diabetes group. Furthermore, the activation of the AKT and mTOR signaling proteins, as well as increased IGF-1 expression, was significantly elevated in the D-T+HIIT group compared to the diabetic control group and other treatment groups, and approached levels observed in the non-diabetes group. Additionally, muscle fiber size and overall tissue structure were improved in the treatment groups, particularly in the D-T+HIIT group. The combination of HIIT and TRF appears to offer superior benefits in improving muscle protein synthesis, and glucose regulation in T2D rats, as compared to either HIIT or TRF alone. These findings highlight the potential of this combined approach for addressing muscle-related complications in T2D.

摘要

高强度间歇训练(HIIT)和限时进食(TRF)已显示出在增强葡萄糖代谢、提高胰岛素敏感性和促进肌肉健康方面的潜力。本研究调查了HIIT和TRF对2型糖尿病(T2D)大鼠肌肉组织中AKT-IGF-1-mTOR信号通路的联合作用。42只雄性Wistar大鼠(4-5周龄)被纳入研究。动物被随机分为两组:1. 标准饮食(SD)非糖尿病组(n = 7)和2. 高脂饮食(HFD,n = 35),持续4周。通过腹腔注射(IP)35 mg/kg链脲佐菌素(STZ)诱导T2D。血糖水平≥250 mg/dL的动物被视为糖尿病大鼠。糖尿病大鼠被随机分为五组(n = 7):1. 糖尿病-HIIT组(D-HIIT),2. 糖尿病-TRF组(D-T),3. 糖尿病-TRF与HIIT联合组(D-T+HIIT),4. 糖尿病未治疗对照组(D),5. 糖尿病二甲双胍治疗组(D-MET)。HIIT方案和TRF方案持续进行10周。收集肌肉组织进行组织学分析,并测量与AKT-IGF-1-mTOR通路相关的蛋白质表达。与非糖尿病组相比,D-T+HIIT组和D-MET组的血糖水平、胰岛素抵抗(IR)和肌肉降解标志物显著改善。此外,与糖尿病对照组和其他治疗组相比,D-T+HIIT组中AKT和mTOR信号蛋白的激活以及IGF-1表达的增加显著升高,并接近非糖尿病组观察到的水平。此外,治疗组的肌纤维大小和整体组织结构得到改善,尤其是D-T+HIIT组。与单独的HIIT或TRF相比,HIIT和TRF的组合似乎在改善T2D大鼠的肌肉蛋白质合成和葡萄糖调节方面具有更大的益处。这些发现突出了这种联合方法在解决T2D中与肌肉相关并发症方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50c3/12073226/e3f0e3d78a0c/nutrients-17-01404-g001.jpg

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