Acute Voluntary Wheel Running Attenuates Olanzapine‐Induced Hyperglycemia in Male Mice
Bibliographic record
Abstract
Background Olanzapine is a second‐generation antipsychotic often used in the treatment of schizophrenia and other “off‐label” conditions. Though effective in reducing psychoses, the use of olanzapine is associated with adverse metabolic side effects. Acutely, olanzapine increases liver glucose output and the development of insulin resistance. Chronic olanzapine treatment leads to weight gain and predisposes individuals to the development of cardiovascular disease and type 2 diabetes. Exercise is an intervention which helps to maintain glucose homeostasis, and with long‐term adherence, can decrease glucose intolerance and insulin resistance. We have previously demonstrated that a single bout of exhaustive exercise mitigates olanzapine‐induced hyperglycemia. While these findings are encouraging, the clinical relevance of exhaustive exercise in individuals taking olanzapine is limited. Purpose & Hypotheses The purpose of this study was to investigate if increases in short‐term, habitual physical activity in the form of voluntary wheel running (VWR) would have a protective effect against olanzapine‐induced hyperglycemia. Methods 10‐week old male C57BL/6J mice remained sedentary or were provided running wheels at the start of the dark cycle (~20:00 h), until the following morning (~8:00 h; start of light cycle). Olanzapine (5 mg/kg body weight (BW)) was administered intraperitoneally (IP) immediately following overnight VWR, or 6 hours and 24 hours post wheel‐lock. Blood glucose was measured at baseline, 30, 60, 90, and 120 mins post‐olanzapine. In parallel experiments following the same overnight VWR protocol, an insulin tolerance test (ITT) (0.5 IU/kg BW; IP) was conducted 60 mins post‐olanzapine treatment to assess olanzapine‐induced insulin resistance among groups. Results A single overnight session of VWR protected against acute olanzapine‐induced hyperglycemia immediately post‐wheel lock. This protective effect was still present 6 hours post‐wheel lock, and had reversed by 24 hours after the cessation of exercise. Under insulin‐stimulated conditions, the sedentary olanzapine‐treated mice had significantly higher blood glucose area‐under‐the‐curve compared to the other three groups, providing evidence that a prior bout of VWR protects against olanzapine‐induced insulin resistance. Under insulin‐stimulated conditions, serum free fatty acid concentrations were increased with olanzapine and reduced with VWR. Conclusions Our findings demonstrate that with a single session of overnight habitual physical activity, olanzapine‐induced hyperglycemia is mitigated for at least 6 hours post‐exercise and insulin‐stimulated glucose disposal is recovered under olanzapine‐treated conditions. Support or Funding Information This study was supported by the Canadian Institutes of Health Research.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".