PPARδ regulates insulin secretion in pancreatic β-cells : evidence from an in-vivo mouse model of β-cell specific PPARδ overexpression
Bibliographic record
Abstract
Onset of obesity-induced type 2 diabetes occurs when pancreatic ~-cells fail to meet the increased insulin demand caused by insulin resistance. Changes in adipose tissue function in obesity results in abnormal deposition of lipids in non-adipose tissues including pancreatic islets. Chronic exposure to fatty acid is lipotoxic to the ~-cells, blunting glucose-stimulated insulin secretion. Peroxisome proliferator activated receptor-~ (PPAR~) belongs to the family of PPAR nuclear transcription factors, key regulators of lipid metabolism. In pancreatic ~-cells PPAR~ has been shown to regulate genes involved in mitochondrial handling of fatty acids causing up regulation of genes involved in mitochondrial fatty acid oxidation. In addition to its role in lipid metabolism, an in-vivo model of ~-cell specific PPAR~ knockout demonstrated a role for PPAR~ in regulating the cellular machinery involved in secretion of insulin granules. Removal of PPAR~ from the ~-cell enhanced second phase insulin secretion due to disassembly of filamentous actin, allowing uninhibited insulin granule secretion. The goal of my project was to determine if the pro-oxidative potential of PPAR~ could protect pancreatic ~-cells from lipotoxicity induced by obesity or if PPAR~\u2019s role in insulin secretion would prevent beneficial effects on ~-cell function. Utilizing an adeno-associated virus (dsAAV8), we induced overexpression of PPAR~ specifically in pancreatic ~-cells of adult C57B16 mice fed a chow or high-fat diet. We observed that overexpression of PPAR~ in pancreatic ~-cells, significantly impairs glucose-stimulated insulin secretion in both lean and obese mice supporting a role for PPAR~ in the regulation of insulin secretory mechanisms. Characterization of filamentous actin, expression and activity of SNARE proteins in ~-cells overexpressing PPAR~ will help to elucidate the mechanism by which PPAR~ results insulin granule exocytosis.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".