Saturated and <i>cis/trans</i> Unsaturated Acyl CoA Esters Differentially Regulate Wild-Type and Polymorphic β-Cell ATP-Sensitive K+ Channels
Bibliographic record
Abstract
Metabolic regulation of pancreatic beta-cell ATP-sensitive K+ channel (K(ATP) channel) function plays a key role in the process of glucose-stimulated insulin secretion (GSIS). Modulation of K(ATP) channel activity by long-chain acyl CoAs represents an important endogenous regulatory mechanism. Elevated acyl CoA levels have been reported in obese and type 2 diabetic individuals and may contribute to reduced beta-cell excitability and impaired GSIS. Recent studies suggest that the composition of dietary fat may influence the effects of high-fat feeding on impaired GSIS. Therefore, we examined the effects of side-chain length and the degree of saturation of various acyl CoAs on K(ATP) channel activity. Macroscopic currents from either wild-type or polymorphic (Kir6.2[E23K/I337V]) recombinant beta-cell K(ATP) channels were measured in inside-out patches by exposing the inner surface of the membrane to acyl CoAs at physiological nanomolar concentrations. Acyl CoAs increased both wild-type and polymorphic K(ATP) channel activity with the following rank order of efficacy: C18:0, C18:1trans approximately C18:1cis, C20:4 = C16:0, C16:1, and C18:2. A significant correlation exists between activation and acyl CoA hydrophobicity, suggesting that both side-chain length and degree of saturation are critical determinants of K(ATP) channel activation. Our observations reveal a plausible mechanism behind the disparate effects of acyl CoA saturation on K(ATP) channel activation and suggest that dietary fat composition may determine the severity of impaired GSIS via differential activation of beta-cell K(ATP) channels.
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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) | 0.001 | 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".