Control of secretory granule access to the plasma membrane by PI3 kinase-γ
Bibliographic record
Abstract
The role and mechanism of phosphatidylinositol 3-OH (PI3) kinase as a regulator of insulin secretion is much debated. Studies employing non-selective pharmacological agents suggest a negative role for this key signal transduction enzyme in insulin release, perhaps through regulation of ATP-sensitive K (+) channels. There are however, three PI3 kinase families containing several kinase isoforms. More recent studies, including our own recently published work, have begun to investigate PI3 kinase isoform-specific mechanisms regulating insulin secretion. Building on our previous work demonstrating that mice lacking a G-protein coupled PI3 kinase catalytic subunit (p110γ -/-) lack first phase insulin secretion and display a blunted second phase of secretion, we have now elucidated the mechanism by which this PI3 kinase isoform acts as a positive regulator of insulin secretion. Using a combined molecular and pharmacological approach, together with biophysical assays of insulin exocytosis and cellular imaging, we demonstrated that p110γ is an important modulator of insulin granule exocytosis and localization to the plasma membrane by modulating cortical actin density.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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) | 0.000 | 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".