Proteomic identification of carboxypeptidase E connects lipid-induced β-cell apoptosis and dysfunction in type 2 diabetes
Bibliographic record
Abstract
Type 2 diabetes occurs when the endocrine pancreas can no longer secrete enough insulin to maintain glucose and lipid homeostasis. This is likely due to cumulative defects in beta-cell fate and function, as well as insulin resistance. A number of recent studies, including ones from our group, have used unbiased proteomic, genomic and genetic approaches to unravel the mechanisms by which hyperlipidemia causes beta-cell apoptosis and dysfunction. It is clear from these studies and others, that there are multiple pathways by which fatty acids such as palmitate can lead to beta-cell dysfunction and death. In the present article, we highlight the role for dysfunction in the ER and secretory pathway in the toxic effects of free fatty acids. Recent work has shown that the rapid degradation of carboxypeptidase E plays a significant role in beta-cell death in response to the free fatty acid palmitate. These newly identified targets of beta-cell lipotoxicity present novel avenues for research and therapeutic intervention.
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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 | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".