Nocturnal activation of melatonin receptor type 1 signaling modulates diurnal insulin sensitivity via regulation of <scp>PI</scp> 3K activity
Bibliographic record
Abstract
Abstract Recent genetic studies have highlighted the potential involvement of melatonin receptor 1 ( MT 1 ) and melatonin receptor 2 ( MT 2 ) in the pathogenesis of type 2 diabetes. Here, we report that mice lacking MT 1 ( MT 1 KO ) tend to accumulate more fat mass than WT mice and exhibit marked systemic insulin resistance. Additional experiments revealed that the main insulin signaling pathway affected by the loss of MT 1 was the activation of phosphatidylinositol‐3‐kinase ( PI 3K). Transcripts of both catalytic and regulatory subunits of PI 3K were strongly downregulated within MT 1 KO mice. Moreover, the suppression of nocturnal melatonin levels within WT mice, by exposing mice to constant light, resulted in impaired PI 3K activity and insulin resistance during the day, similar to what was observed in MT 1 KO mice. Inversely, administration of melatonin to WT mice exposed to constant light was sufficient and necessary to restore insulin‐mediated PI 3K activity and insulin sensitivity. Hence, our data demonstrate that the activation of MT 1 signaling at night modulates insulin sensitivity during the day via the regulation of the PI 3K transcription and activity. Lastly, we provide evidence that decreased expression of MTNR 1A ( MT 1 ) in the liver of diabetic individuals is associated with poorly controlled diabetes.
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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 | 0.005 | 0.013 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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".