The Role of Estrogen and ER Stress in Glycemic Regulation in the Sexually Dimorphic TALLYHO/JngJ Mouse Model of Diabetes
Bibliographic record
Abstract
The global incidence of diabetes mellitus is increasing, causing a heavy burden on health care management and costs. Sex differences in the incidence and prevalence of diabetes mellitus do exist, with premenopausal women being protected from developing this disease, compared to men or postmenopausal women. The mechanisms underlying these differences are not yet known and experimental animal models can significantly advance our understanding of these processes. In this study we characterized a mouse model of polygenic type 2 diabetes, the TALLYHO/JngJ mouse, which shows sexual dimorphism in blood glucose regulation. Male TALLYHO/JngJ mice develop chronic hyperglycemia by 5 weeks of age, while females remain normoglycemic. We analyzed the role of endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR) in the development of hyperglycemia in this mouse model. Additionally, we evaluated the effect of estrogen depletion in female TALLYHO/JngJ mice through ovariectomies. Ovariectomized female mice and males become chronically hyperglycemic (fasting blood glucose threshold >15 mM) and show significantly increased expression of GRP78/GRP94, markers of the adaptive unfolded protein response (UPR). GADD153/CHOP, a marker of the apoptotic UPR, is significantly increased in ovariectomized female mice. Treatment with a chemical chaperone 4-PBA, an ER stress alleviator, improves but does not normalize blood glucose levels in male and ovariectomized female TALLYHO/JngJ mice. Together, these findings support a protective role for estrogen and identify the UPR as a pathway through which estrogen may maintain pancreatic beta cell health.
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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) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".