Diabetic myopathy differs between<i>Ins2</i><sup><i>Akita+/−</i></sup>and streptozotocin-induced Type 1 diabetic models
Bibliographic record
Abstract
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 microm(2)) and STZ (1,768 +/- 163 microm(2)) compared with control (2,241 +/- 144 microm(2)). Conversely, STZ type I fibers (1,535 +/- 165 microm(2)) were significantly larger than Ins2(Akita+/-) (915 +/- 76 microm(2)) but not control (1,152 +/- 86 microm(2)). 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 micromol.s(-1).mg(-1); Ins2(Akita+/-): 5.2 +/- 0.8 micromol.s(-1).mg(-1); STZ: 2.8 +/- 0.5 micromol.s(-1).mg(-1)) and 3-beta-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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".