Mitochondrial metabolism and dynamics in pancreatic beta cell glucose sensing
Bibliographic record
Abstract
Glucose-regulated insulin secretion becomes defective in all forms of diabetes. The signaling mechanisms through which the sugar acts on the ensemble of beta cells within the islet remain a vigorous area of research after more than 60 years. Here, we focus firstly on the role that the privileged oxidative metabolism of glucose plays in glucose detection, discussing the importance of 'disallowing' in the beta cell the expression of genes including Lactate dehydrogenase (Ldha) and the lactate transporter Mct1/Slc16a1 to restrict other metabolic fates for glucose. We next explore the regulation of mitochondrial metabolism by Ca2+ and its possible role in sustaining glucose signaling towards insulin secretion. Finally, we discuss in depth the importance of mitochondrial structure and dynamics in the beta cell, and their potential for therapeutic targeting by incretin hormones or direct regulators of mitochondrial fusion. This review, and the 2023 Sir Philip Randle Lecture which GAR will give at the Islet Study Group meeting in Vancouver, Canada in June 2023, honor the foundational, and sometimes under-appreciated, contributions made by Professor Randle and his colleagues towards our understanding of the regulation of insulin secretion.
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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) | 0.002 | 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 | 0.001 |
| 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".