Exercise modality-dependent non-hypertrophic anabolic adaptations in skeletal muscle of rats with type 2 diabetes

Type 2 diabetes mellitus (T2DM) is frequently accompanied by progressive skeletal muscle loss and dysfunction, commonly referred to as diabetic sarcopenia. Exercise is an established non-pharmacological therapy for T2DM; however, how different exercise modalities differentially influence skeletal muscle protein regulation and anabolic signaling remains unclear. This study compared the effects of aerobic exercise, resistance exercise, and their combination on skeletal muscle protein content and irisin-associated anabolic signaling in a rat model of T2DM.

Male rats with diet- and streptozotocin-induced T2DM were assigned to aerobic exercise, resistance exercise, combined aerobic-resistance exercise, or sedentary diabetic control for 8 weeks. Metabolic indices, skeletal muscle mass and morphology, and molecular markers related to muscle protein content, proteolytic signaling, and anabolic pathways were assessed using biochemical, histological, and protein expression analyses.

Diabetic rats exhibited impaired metabolic profiles, reduced skeletal muscle mass and protein content, and increased muscle fibrosis. All exercise modalities improved selected metabolic indices. Exercise intervention significantly increased skeletal muscle protein content across all exercise groups, despite minimal changes in muscle fiber cross-sectional area and no detectable suppression of canonical ubiquitin-proteasome atrophy markers. Resistance-containing exercise modalities showed greater engagement of integrin α7β1 and PI3K-related signaling components, whereas AKT and mTOR responses were observed across exercise modalities. Exercise increased skeletal muscle irisin expression.

Exercise intervention in diabetic skeletal muscle induces a non-hypertrophic anabolic adaptation characterized by increased muscle protein content and patterned activation of anabolic signaling pathways. Resistance-containing exercise preferentially engaged select mechanotransduction-related signaling components without conferring global superiority across outcomes.