HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 106/5/1650    most recent 91565.2008v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Krause, M. P. Articles by Hawke, T. J. Search for Related Content PubMed PubMed Citation Articles by Krause, M. P. Articles by Hawke, T. J.

Diabetic myopathy differs between Ins2^Akita+/– and streptozotocin-induced Type 1 diabetic models

¹Department of Pathology and Molecular Medicine, McMaster University, Hamilton; and ²School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada

Submitted 3 December 2008 ; accepted in final form 20 February 2009

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.

insulin-dependent diabetes mellitus; muscle lipids; fiber-type shift; muscle stimulation; capillary-to-fiber ratio; twitch force