Distinctive phenotypic, metabolic and contractile properties of Ins2Akita+/− and streptozotocin‐induced diabetic skeletal muscles.

The impact of type 1 diabetes on skeletal muscle (diabetic myopathy) during adolescence is largely unknown. Diabetic myopathy studies commonly use streptozotocin‐induced diabetic (STZ) rodents; however, streptozotocin has known detrimental effects on muscle cell growth. Here, we examined mechanisms of diabetic myopathy in adolescent Akita and STZ mice following 8 weeks of diabetes. Both models exhibited reduced muscle mass (Akita: 0.124 ± 0.008g; STZ: 0.124 ± 0.024g; Con: 0.162 ± 0.015g) and IIB/D fiber area (Akita: 57.7 ± 4.2% and STZ: 78.9 ± 7.3% of Con). Intramyocellular lipid was increased in STZ (122.9 ± 3.6% of Con) but not Akita muscle, resulting from lower citrate synthase and β‐HAD activities in STZ muscle. Functional analyses revealed lower absolute peak force in Akita (70.2 ± 8.2% of Con) but not STZ muscle (87.6 ± 7.9% of Con). Corrected for muscle mass, no relative force difference was observed between Akita and Con, while STZ relative force was significantly elevated. STZ muscle exhibits contractile, metabolic and phenotypic properties distinct from Akita, despite similarity in hyperglycemia, furthering concerns of toxic effects of streptozotocin on muscle. In Akita mice, muscle atrophy and specific fiber type loss did not affect contractile properties (relative to muscle mass), suggesting that pathological metabolic changes within diabetic muscle precede alteration of contractile properties.