Lowering insulin mitigates female reproductive aging and diet-induced ovarian dysfunction
Bibliographic record
Abstract
Abstract Hyperinsulinemia has consequences beyond metabolic dysfunction, including reproductive system effects. We found that hyperinsulinemia at age 46-47 was predictive of earlier menopause in the Study of Women’s Health Across the Nation. To test causality between insulin levels and reproductive aging, we longitudinally evaluated chow- or high-fat, high-sucrose (HFHS)-fed Ins1 -null female mice with full or partial Ins2 insulin gene expression. Ins1 -/- ;Ins2 +/- mice had lower HFHS-induced hyperinsulinemia and less weight gain than their full- Ins2 littermates, despite comparable HFHS-induced glucose intolerance up to 9 months. By 15 months, Ins1 -/- ;Ins2 +/+ ovaries showed multinucleated giant cell accumulation with HFHS, while Ins1 -/- ;Ins2 +/- mice were protected against this response and maintained a higher reserve of follicles. Moreover, aged Ins1 -/- ;Ins2 +/- mice were 9-fold more likely to conceive on HFHS than hyperinsulinemic Ins1 -/- ;Ins2 +/+ mice. Elevated insulin is therefore a critical mechanistic link between metabolic dysfunction and reproductive aging, and curtailing insulin levels protects against subfertility and HFHS-induced ovarian decline.
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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) | 0.000 | 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) | 0.002 | 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".