Prohormone convertase 1/3 deficiency causes obesity due to impaired proinsulin processing
Bibliographic record
Abstract
Defective insulin processing is associated with obesity and diabetes. Prohormone convertase 1/3 (PC1/3) is an endopeptidase required for the processing of neurotransmitters and hormones. PC1/3 deficiency and genome-wide association studies relate PC1/3 with early onset obesity. Here, we find that deletion of PC1/3 in obesity-related neuronal cells expressing proopiomelanocortin mildly and transiently change body weight and fail to produce a phenotype when targeted to Agouti-related peptide- or nestin-expressing tissues. In contrast, pancreatic β cell-specific PC1/3 ablation induces hyperphagia with consecutive obesity despite uncontrolled diabetes with glucosuria. Obesity develops not due to impaired pro-islet amyloid polypeptide processing but due to impaired insulin maturation. Proinsulin crosses the blood-brain-barrier but does not induce central satiety. Accordingly, insulin therapy prevents hyperphagia. Further, islet PC1/3 expression levels negatively correlate with body mass index in humans. In this work, we show that impaired PC1/3-mediated proinsulin processing, as observed in human prediabetes, promotes hyperphagic obesity.
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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 | 0.001 | 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 | 0.001 |
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".