Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, 739-8528, Japan.
Graduate School of Humanities and Social Sciences, Hiroshima University, Hiroshima, 739-8521, Japan.
Acta Diabetol. 2024 Nov;61(11):1443-1453. doi: 10.1007/s00592-024-02311-3. Epub 2024 Jun 10.
Streptozotocin (STZ) is widely used to study diabetic complications. Owing to the nonspecific cytotoxicity of high-dose STZ, alternative models using moderate-dose or a combination of low-dose STZ and a high-fat diet have been established. This study aimed to investigate the effects of these models on muscle function.
The muscle function of two STZ models using moderate-dose STZ (100 mg/kg, twice) and a combination of low-dose STZ and high-fat diet (50 mg/kg for 5 consecutive days + 45% high-fat diet) were examined using in vivo electrical stimulation. Biochemical and gene expression analysis were conducted on the skeletal muscles of the models immediately after the stimulation.
The contractile force did not differ significantly between the models compared to respective controls. However, the moderate-dose STZ model showed more severe fatigue and blunted exercise-induced glycogen degradation possibly thorough a downregulation of oxidative phosphorylation- and vasculature development-related genes expression.
Moderate-dose STZ model is suitable for fatigability assessment in diabetes and careful understanding on the molecular signatures of each model is necessary to guide the selection of suitable models to study diabetic myopathy.
链脲佐菌素(STZ)被广泛用于研究糖尿病并发症。由于高剂量 STZ 的非特异性细胞毒性,已经建立了使用中剂量或低剂量 STZ 与高脂肪饮食相结合的替代模型。本研究旨在探讨这些模型对肌肉功能的影响。
使用中剂量 STZ(100mg/kg,两次)和低剂量 STZ 与高脂肪饮食相结合(50mg/kg,连续 5 天+45%高脂肪饮食)的两种 STZ 模型的肌肉功能通过体内电刺激进行检测。刺激后立即对模型的骨骼肌进行生化和基因表达分析。
与各自的对照组相比,两种模型的收缩力没有显著差异。然而,中剂量 STZ 模型表现出更严重的疲劳和运动引起的糖原降解迟钝,可能是通过下调氧化磷酸化和血管发育相关基因的表达。
中剂量 STZ 模型适合评估糖尿病的疲劳性,需要仔细了解每种模型的分子特征,以指导选择合适的模型来研究糖尿病性肌病。