Sympathetic decentralization after spinal cord injury spares Zucker Diabetic Fatty rats from frank diabetes
Bibliographic record
Abstract
Introduction Metabolic syndrome, characterized by the constellation of visceral obesity, atherogenic dyslipidemia, proinflammatory state, hypertension, and insulin resistance, confers a 5‐fold increase in the risk of type 2 diabetes (T2D). Accumulating data from human and animal studies revealed a strong association between sympathetic nervous system (SNS) activation and different components of metabolic syndrome, such as obesity, hypertension, and insulin resistance. However, it is not clear whether sympathoexcitation is a cause or result of metabolic syndrome and the subsequent T2D. Here we used high thoracic spinal cord injury (SCI) as an effective means for SNS decentralization in order to investigate the potential role of the SNS in the pathogenesis of T2D in an animal model of metabolic syndrome. Method/Design Eighteen male Zucker Diabetic Fatty rats (ZDF‐Lepr fa/fa , Metabolic syndrome/T2D animal model) were evenly assigned to two groups: uninjured (Fatty‐Sham), and T3 complete SCI (Fatty‐SCI). Lean Zucker Diabetic Fatty rats (ZDF‐Lepr + , n = 9) acted as controls. T2D development was evaluated using biweekly random blood glucose measurements and oral glucose tolerance test (OGTT) at week 11 post‐injury. Twelve weeks post‐injury, animals were euthanized and blood samples and pancreas tissue were collected for further analyses. Results We found that SCI‐induced SNS decentralization, manifested by a dramatic decline in plasma norepinephrine (P = 0.011), was accompanied by improved glucose tolerance, i.e. decreased glucose area under the curve (AUC, P = 0.001), increased fasting insulin (1.00 ± 0.33 vs. 3.02 ± 1.5 ng/ml, p = 0.011), and augmented insulin response after an OGTT, i.e. increased insulin AUC (P = 0.001) in the Fatty‐SCI group compared to uninjured Fatty‐Sham group. Although Fatty‐Sham and Fatty‐SCI groups exhibited a comparable degree of insulin resistance, Fatty‐SCI had significantly higher β‐cell activity indicated by a significant increase in homeostatic model assessment‐%B (HOMA‐%B) index (P = 0.0064). Pancreatic gene expression analysis revealed that SCI caused a significant reduction in the local expression of inflammatory mediators, i.e. IL‐1β and TNF‐α, which are critical for inhibition of insulin secretion, and induction of β‐cell apoptosis and dysfunction. While SNS decentralization spared the Fatty‐SCI rats from frank diabetes, Fatty‐SCI and Fatty‐Sham rats both exhibited other components of metabolic syndrome, including abdominal obesity and dyslipidemia, as compared to lean rats. Support or Funding Information This work has been supported by Michael Smith Foundation for Health Research, Craig H. Neilsen Foundation, Heart and Stroke Foundation of Canada, and the International Collaboration on Repair Discoveries.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".