Kv2.1 regulates insulin secretion in human islets independent of it's electrical function
Bibliographic record
Abstract
The voltage-dependent K+ (Kv) channel Kv2.1 mediates a major portion of the K+ current contributing to β-cell action potential repolarization, and also interacts with exocytotic SNARE proteins including syntaxin 1A. We now show that Kv2.1 modulates β-cell exocytosis and insulin secretion independent of its role in conducting K+. Expression of a non-conducting Kv2.1 pore mutant (W365C/Y380T) directly augmented the exocytotic response of human β-cells assessed by whole-cell capacitance. Acute intracellular dialysis, or transient expression, of an intracellular C-terminal fragment of Kv2.1 (C1; amino acids 412–633) which disrupts the channel interaction with syntaxin 1A inhibited the exocytotic response to membrane depolarization by 70–79% (p<0.001), whereas distal C-terminal (C2; aa 634–853) or N-terminal (aa 1–182) fragments had no effect. The Kv2.1-C1 fragment also inhibited glucose-stimulated insulin secretion from human islets, but did not affect secretory granule localization to the plasma membrane. These findings demonstrate a role for Kv2.1 in insulin secretion, by facilitating insulin granule exocytosis independent of its K+ conductance.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".