Overcoming the spatial barriers of the stimulus secretion cascade in pancreatic β-cells
Bibliographic record
Abstract
The ability of the pancreatic β-cells to adapt the rate of insulin release in accordance to changes in circulating glucose levels is essential for glucose homeostasis. Two spatial barriers imposed by the plasma membrane and inner mitochondrial membrane need to be overcome in order to achieve stringent coupling between the different steps in the stimulus-secretion cascade. The first spatial barrier is overcome by the presence of a glucose transporter (GLUT) in the plasma membrane, whereas a low affinity hexokinase IV (glucokinase, GK) in the cytosol conveys glucose availability into a metabolic flux that triggers and accelerates insulin release. The mitochondrial inner membrane comprises a second spatial barrier that compartmentalizes glucose metabolism into glycolysis (cytosol) and tricarboxylate (TCA) cycle (mitochondrial matrix). The exchange of metabolites between cytosol and mitochondrial matrix is mediated via a set of mitochondrial carriers, including the aspartate-glutamate carrier (aralar1), α- ketoglutarate carrier (OGC), ATP/ADP carrier (AAC), glutamate carrier (GC1), dicarboxylate carrier (DIC) and citrate/isocitrate carrier (CIC). The scope of this review is to provide an overview of the role these carriers play in stimulus-secretion coupling and discuss the importance of these findings in the context of the exquisite glucose responsive state of the pancreatic β-cell.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".