Submitted on December 3, 2008
Revised on February 18, 2009
Accepted on February 20, 2009
Diabetic myopathy differs between Ins2Akita+/- and streptozotocin-induced type 1 diabetic models
Matthew P. Krause1, Michael C. Riddell1, Carly S. Gordon1, S. Abdullah Imam1, Enzo Cafarelli1, and Thomas J. Hawke2*
1 York University
2 McMaster University
* To whom correspondence should be addressed. E-mail: thawke{at}yorku.ca.
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, Ins2Akita+/- mice and contrast these findings with STZ mice. Eight weeks of diabetes resulted in significantly reduced gastrocnemius/plantaris/soleus mass (Control: 0.16±0.005g; Ins2Akita+/-: 0.12±0.003g; STZ: 0.12±0.01g) and IIB/D fiber area in Ins2Akita+/- (1294±94µm2) and STZ (1768±163µm2) compared to Control (2241±144µm2). Conversely, STZ type I fibers (1535±165µm2) were significantly larger than Ins2Akita+/- (915±76µm2) but not Control (1152±86µm2). Intramyocellular lipid increased in STZ (122.9±3.6% of Control) but not Ins2Akita+/- likely resultant from depressed citrate synthase (Control: 6.2±1.2µmol.s-1.g-1; Ins2Akita+/-: 5.2±0.8µmol.s-1.g-1; STZ: 2.8±0.5µmol.s-1.g-1) and 
-HAD (Control: 4.2±0.6nmol.s-1.g-1; Ins2Akita+/-: 5.0±0.6nmol.s-1.g-1; STZ: 2.7±0.6nmol.s-1.g-1) enzyme activity in STZ muscle. In situ muscle stimulation revealed lower absolute peak tetanic force in Ins2Akita+/- (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 Ins2Akita+/-, while STZ was significantly elevated versus Control and Ins2Akita+/-. These results demonstrate that atrophy and specific fiber type loss in Ins2Akita+/- muscle did not affect contractile properties (relative to muscle mass). Furthermore, we demonstrate distinctive contractile, metabolic and phenotypic properties in STZ versus Ins2Akita+/- diabetic muscle despite similarity in hyperglycemia/hypoinsulinemia, raising concerns of our current state of knowledge regarding the effects of T1DM on skeletal muscle.
