A peripherally restricted cannabinoid-1 receptor inverse agonist promotes insulin secretion and protects from cytokine toxicity in human pancreatic islets
Bibliographic record
Abstract
The cannabinoid receptor CB1R is expressed in pancreatic β-cells; CB1R increased activity is associated with diabetes, obesity, cardiovascular disorders as well as decreased insulin secretion and insulin resistance. CB1R was shown to signal through G-protein coupling as well as β-arrestins in β-cells. Peripherally restricted CB1R inverse agonists purportedly have beneficial effects on insulin secretion in β-cells, without the unwanted effects in the central nervous system. Here we show that a peripherally restricted CB1R inverse agonist, MRI-1891, augments glucose stimulated insulin secretion in isolated human pancreatic islets and mouse islets. The insulin secretion enhancing effect of MRI-1891 is comparable to exendin-4, an analogue of the glucagon like peptide-1 (GLP1). Moreover, MRI-1891 treatment protects isolated human islet cells against cytokine-induced apoptosis, similar to exendin-4. Thus, MRI-1891, a new class of CB1R inverse agonist, may be considered a potential therapeutic for both type 1 and type 2 diabetes because of its ability to protect pancreatic β-cells from cytokine toxicity and to promote insulin secretion.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".