Diabetic myopathy differs between Ins2Akita+/− and streptozotocin-induced Type 1 diabetic models Academic Article uri icon

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  • Mechanistic studies examining the effects of Type 1 diabetes mellitus (T1DM) on skeletal muscle have largely relied on streptozotocin-induced diabetic (STZ) rodents. Unfortunately, characterization of diabetic myopathy in this model is confounded by the effects of streptozotocin on skeletal muscle independent of the diabetic phenotype. Here we define adolescent diabetic myopathy in a novel, genetic model of T1DM, Ins2 Akita+/− mice, and contrast these findings with STZ mice. Eight weeks of diabetes resulted in significantly reduced gastrocnemius-plantaris-soleus mass (control: 0.16 ± 0.005 g; Ins2 Akita+/−: 0.12 ± 0.003 g; STZ: 0.12 ± 0.01g) and IIB/D fiber area in Ins2 Akita+/− (1,294 ± 94 μm2) and STZ (1,768 ± 163 μm2) compared with control (2,241 ± 144 μm2). Conversely, STZ type I fibers (1,535 ± 165 μm2) were significantly larger than Ins2 Akita+/− (915 ± 76 μm2) but not control (1,152 ± 86 μm2). Intramyocellular lipid increased in STZ (122.9 ± 3.6% of control) but not Ins2 Akita+/− likely resultant from depressed citrate synthase (control: 6.2 ± 1.2 μmol·s−1·mg−1; Ins2 Akita+/−: 5.2 ± 0.8 μmol·s−1·mg−1; STZ: 2.8 ± 0.5 μmol·s−1·mg−1) and 3-β-hydroxyacyl coenzyme-A dehydrogenase (control: 4.2 ± 0.6 nmol·s−1·mg−1; Ins2 Akita+/−: 5.0 ± 0.6 nmol·s−1·mg−1; STZ: 2.7 ± 0.6 nmol·s−1·mg−1) enzyme activity in STZ muscle. In situ muscle stimulation revealed lower absolute peak tetanic force in Ins2 Akita+/− (70.2 ± 8.2% of control) while STZ exhibited an insignificant decrease (87.6 ± 7.9% of control). Corrected for muscle mass, no force loss was observed in Ins2 Akita+/−, while STZ was significantly elevated vs. control and Ins2 Akita+/−. These results demonstrate that atrophy and specific fiber-type loss in Ins2 Akita+/− muscle did not affect contractile properties (relative to muscle mass). Furthermore, we demonstrate distinctive contractile, metabolic, and phenotypic properties in STZ vs. Ins2 Akita+/− diabetic muscle despite similarity in hyperglycemia/hypoinsulinemia, raising concerns of our current state of knowledge regarding the effects of T1DM on skeletal muscle.


  • Krause, Matthew P
  • Riddell, Michael C
  • Gordon, Carly S
  • Imam, S Abdullah
  • Cafarelli, Enzo
  • Hawke, Thomas

publication date

  • May 2009