Adaptation to Mild, Intermittent Stress Delays Development of Hyperglycemia in the Zucker Diabetic Fatty Rat Independent of Food Intake: Role of Habituation of the Hypothalamic-Pituitary-Adrenal Axis
Bibliographic record
Abstract
Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity occurs in type 2 diabetes, and stress is assumed to play a causal role. However, intermittent restraint stress, a model mimicking some mild stressors, delays development of hyperglycemia in Zucker diabetic fatty (ZDF) rats. We examine whether such stress delays hyperglycemia independent of stress-induced reductions in hyperphagia and is due to adaptations in gene expression of HPA-related peptides and receptors that ameliorate corticosteronemia and thus hyperglycemia. ZDF rats were intermittently restraint stressed (1 h/d, 5 d/wk) for 13 wk and compared with obese control, pair fed, and lean ZDF rats. After 13 wk, basal hormones were repeatedly measured over 24 h, and HPA-related gene expression was assessed by in situ hybridization. Although restraint initially induced hyperglycemia, this response habituated over time, and intermittent restraint delayed hyperglycemia. This delay was partly related to 5-15% decreased hyperphagia, which was not accompanied by decreased arcuate nucleus NPY or increased POMC mRNA expression, although expression was altered by obesity. Obese rats demonstrated basal hypercorticosteronemia and greater corticosterone responses to food/water removal. Basal hypercorticosteronemia was further exacerbated after 13 wk of pair feeding during the nadir. Importantly, intermittent restraint further delayed hyperglycemia independent of food intake, because glycemia was 30-40% lower than after 13 wk of pair feeding. This may be mediated by increased hippocampal MR mRNA, reduced anterior pituitary POMC mRNA levels, and lower adrenal sensitivity to ACTH, thus preventing basal and stress-induced hypercorticosteronemia. In contrast, 24-h catecholamines were unaltered. Thus, rather than playing a causal role, intermittent stress delayed deteriorations in glycemia and ameliorated HPA hyperactivity in the ZDF rat.
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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) | 0.000 | 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) | 0.001 | 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 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".