Increased KATP channel current in pancreatic beta cells over expressing fatty acyl CoA synthetase I
Bibliographic record
Abstract
Closure of KATP channels links glucose metabolism to enhanced electrical activity and insulin secretion in the pancreatic beta cell. Long chain acyl CoAs can potently activate KATP when perfused directly across excised membrane patches, which could account for impaired glucose‐stimulated insulin secretion in obese and type II diabetic individuals via reduced beta cell excitability. However, the effects of chronic elevation of acyl CoAs within beta cells have not been documented. We have enhanced endogenous acyl CoA levels within intact primary mouse beta cells using virally delivered over expression of fatty acyl CoA synthetase‐1 (FACS‐1), and assessed the effects of this manipulation on beta cell excitability using the perforated whole‐cell patch‐clamp technique. Infection with AdFACS‐1 produced a large increase in FACS‐1 protein expression compared to controls (AdGFP‐treated), as confirmed by Western blot. Patch‐clamp data indicated a significant enhancement (p<0.05, n=7) of basal KATP current measured at low glucose in AdFACS‐1 infected cells compared to controls. Furthermore, membrane potential recordings showed a decreased spiking frequency in response to high glucose in AdFACS‐1 infected cells. We provide direct evidence for reduced beta cell excitability by a FACS‐1 driven cytosolic accumulation of acyl CoAs. These observations suggest a strong and direct link between intracellular fatty esters and KATP activity and may have major implications for our current understanding of the involvement of diet and obesity in the development of type II diabetes. Work is sponsored by CIHR and AHFMR.
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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) | 0.001 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".