Impaired insulin secretion in transgenic mice over-expressing calpastatin in pancreatic β-cells
Bibliographic record
Abstract
Calpains are a family of calcium-activated proteases involved in a number of cellular functions including cell death, proliferation and exocytosis. The finding that variation in the calpain-10 gene increases type 2 diabetes risk in some populations has increased interest in determining the potential role of calpains in pancreatic β-cell function. In the present study, transgenic mice (Cast (RIP)) expressing an endogenous calpain inhibitor, calpastatin, in pancreatic β-cells were used to dissect the role of the calpain system in the regulation insulin secretion in vivo and in vitro. Glucose concentrations after the administration of intraperitoneal glucose were significantly increased in Cast (RIP) mice compared with wildtype littermate controls. This was associated with a reduction in glucose-stimulated insulin secretion in vivo. Using pancreas perfusion, static islet incubation and islet perifusion, it was demonstrated that Cast (RIP) islets hypersecreted insulin at low glucose, but exhibited significantly impaired insulin responses to high glucose. Examination of insulin release and calcium signals from isolated islets indicated that distal components of the insulin exocytotic pathway were abnormal in Cast (RIP) mice. Cast (RIP) islets had modestly reduced expression of Rab3a and other critical components in the late steps of insulin exocytosis. These studies provide the first evidence that blocking endogenous calpain activity partially impairs insulin release in vivo and in vitro by targeting distal components of the insulin exocytotic machinery.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| 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".