Abnormal glucose homeostasis in adult female rat offspring after intrauterine ethanol exposure
Bibliographic record
Abstract
Adverse events during pregnancy, including prenatal ethanol (EtOH) exposure, are associated with insulin-resistant diabetes in male rat offspring, but it is unclear whether this is true for female offspring. We investigated whether prenatal EtOH exposure alters glucose metabolism in adult female rat offspring and whether this is associated with reduced in vivo insulin signaling in skeletal muscle. Female Sprague-Dawley rats were given EtOH, 4 g.kg(-1).day(-1) by gavage throughout pregnancy. Glucose tolerance test and hyperinsulinemic euglycemic clamp were performed, and insulin signaling was investigated in skeletal muscle, in adult female offspring. We gave insulin intravenously to these rats and determined the association of glucose transporter-4 with plasma membranes, as well as the phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1), Akt, and PKCzeta. Although EtOH offspring had normal birth weight, they were overweight as adults and had fasting hyperglycemia, hyperinsulinemia, and reduced insulin-stimulated glucose uptake. After insulin treatment, EtOH-exposed rats had decreased membrane glucose transporter-4, PDK1, Akt, and PKCzeta in the gastrocnemius muscle, compared with control rats. Insulin stimulation of PDK1, Akt, and PKCzeta phosphorylation was also reduced. In addition, the expression of the protein tribbles-3 and the phosphatase enzyme activity of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), which prevent Akt activation, were increased in muscle from EtOH-exposed rats. Female rat offspring exposed to EtOH in utero develop insulin-resistant diabetes in association with excessive PTEN and tribbles-3 signaling downstream of the phosphatidylinositol 3-kinase pathway in skeletal muscle, which may be a mechanism for the abnormal glucose tolerance.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".