Why the study?
Alternative moderate-dose and low-dose STZ plus high-fat diet models were established to avoid the nonspecific cytotoxicity of high-dose STZ, but their effects on muscle function needed investigation.
Moderate-dose streptozotocin induces more severe muscle fatigue and mitochondrial dysfunction than low-dose streptozotocin with a high-fat diet, highlighting its utility for studying fatigability in diabetic myopathy.
Moderate-dose streptozotocin model may better capture diabetic myopathy fatigue; animal data leaves open human translation.
AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Aisyah et al. (2024) studied Streptozotocin-induced diabetes. Moderate-dose STZ vs low-dose STZ + high-fat diet vs. Respective controls was evaluated on Muscle function (contractile force and fatigue).
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