Faculty of Sport and Health Science, Ritsumeikan University, Kusatsu, Shiga, Japan.
Research Fellow of Japan Society for the Promotion of Science, Chiyoda-ku, Tokyo, Japan.
Physiol Rep. 2021 May;9(9):e14823. doi: 10.14814/phy2.14823.
Chronic resistance exercise induces improved hyperglycemia in patients with type 2 diabetes mellitus. Musclin, a muscle-derived secretory factor, is involved in the induction of insulin resistance via the downregulation of the glucose transporter-4 (GLUT-4) signaling pathway in skeletal muscles. However, whether musclin affects the mechanism of resistance exercise remains unclear. This study aimed to clarify whether decreased muscle-derived musclin secretion in chronic resistance exercise is involved in the improvement of insulin resistance via the GLUT-4 signaling pathway in rats with type 2 diabetes. Male, 20-week-old, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model, were randomly divided into two groups: sedentary control (OLETF-Con) and chronic resistance exercise (OLETF-RT; climbing a ladder three times a week on alternate days for 8 weeks), whereas Long-Evans Tokushima Otsuka rats were used as the nondiabetic sedentary control group. OLETF-Con rats showed increased fasting glucose levels, decreased insulin sensitivity index (QUICKI), muscle GLUT-4 translocation, and protein kinase B (Akt) phosphorylation, and concomitantly increased muscle musclin expression. In contrast, OLETF-RT rats significantly reduced muscle musclin expression, improved hyperglycemia, and QUICKI through an accelerated muscle GLUT-4/Akt signaling pathway. Moreover, chronic resistance exercise-induced reduction of muscle musclin was correlated with changes in fasting glucose, QUICKI, GLUT-4 translocation, and Akt phosphorylation. These findings suggest that the reduction in muscle-derived musclin production by chronic resistance exercise may be involved in improved insulin resistance in rats with type 2 diabetes.
慢性抗阻运动可改善 2 型糖尿病患者的高血糖。肌肉分泌因子肌联蛋白（Musclin）通过下调骨骼肌葡萄糖转运蛋白 4（GLUT-4）信号通路参与诱导胰岛素抵抗。然而，肌联蛋白是否影响抗阻运动的机制尚不清楚。本研究旨在阐明慢性抗阻运动中肌肉来源的肌联蛋白分泌减少是否通过 2 型糖尿病大鼠的 GLUT-4 信号通路参与改善胰岛素抵抗。雄性，20 周龄，Otsuka Long-Evans Tokushima Fatty（OLETF）大鼠，2 型糖尿病模型，随机分为两组：安静对照组（OLETF-Con）和慢性抗阻运动组（OLETF-RT；每周 3 次，隔日进行，持续 8 周，攀爬梯子），而 Long-Evans Tokushima Otsuka 大鼠作为非糖尿病安静对照组。OLETF-Con 大鼠表现为空腹血糖升高、胰岛素敏感指数（QUICKI）降低、肌肉 GLUT-4 易位和蛋白激酶 B（Akt）磷酸化降低，同时肌肉肌联蛋白表达增加。相反，OLETF-RT 大鼠通过加速肌肉 GLUT-4/Akt 信号通路显著降低肌肉肌联蛋白表达，改善高血糖和 QUICKI。此外，慢性抗阻运动诱导的肌肉肌联蛋白减少与空腹血糖、QUICKI、GLUT-4 易位和 Akt 磷酸化的变化相关。这些发现表明，慢性抗阻运动引起的肌肉源性肌联蛋白产生减少可能参与改善 2 型糖尿病大鼠的胰岛素抵抗。
