14-3-3z constrains insulin secretion by regulating mitochondrial function in pancreatic b-cells
Bibliographic record
Abstract
While critical for neurotransmitter synthesis, 14-3-3 proteins are often assumed to have redundant\nfunctions due to their ubiquitous expression, but despite this assumption, various 14-3-3 isoforms have\nbeen implicated in regulating metabolism. We previously reported contributions of 14-3-3z in b-cell\nfunction, but these studies were performed in tumor-derived MIN6 cells and systemic knockout mice. To\nfurther characterize the regulatory roles of 14-3-3-z in b-cell function, we generated b-cell-specific 14-3-3z\nknockout mice. Although no effects on b-cell mass were detected, potentiated glucose-stimulated insulin\nsecretion (GSIS), mitochondrial function, and ATP synthesis were observed. 14-3-3z deletion also altered\nthe b-cell transcriptome, as genes associated with mitochondrial respiration and oxidative phosphorylation\nwere upregulated. Acute 14-3-3 protein inhibition in mouse and human islets recapitulated the\nenhancements in GSIS and mitochondrial function, suggesting that 14-3-3z is the critical isoform in bcells. In dysfunctional db/db islets and human islets from type 2 diabetic donors, expression of\nYwhaz/YWHAZ, the gene encoding 14-3-3z, was inversely associated with insulin secretion, and pan-14-\n3-3 protein inhibition led to enhanced GSIS and mitochondrial function. Taken together, this study\ndemonstrates important regulatory functions of 14-3-3z in the regulation of b-cell function and provides a\ndeeper understanding of how insulin secretion is controlled in b-cells.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 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".