1843-P: Regulator of G Protein Signaling 9 (RGS9) Is a Positive Regulator of Insulin Secretion in Mouse Islets
Bibliographic record
Abstract
Introduction and Objective: Beta-cell function and mass are under control of G protein-coupled receptors (GPCRs) which are themselves subject to intracellular regulation by regulator of G protein signaling (RGS) proteins. Although the importance of GPCRs to beta-cell biology is well documented, the role of RGS proteins is largely unknown. Recent evidence suggests that RGS9 may have a role in the control of beta-cell function. The aim of this study was to better understand how RGS9 regulates insulin secretion. Methods: Quantitative (q) PCR and RNA in situ hybridization were performed on isolated male mouse islets and pancreatic sections, respectively. Male mouse pseudoislets were infected with adenoviruses encoding short-hairpin (sh) RNAs against RGS9 or control viruses. Glucose-stimulated insulin secretion (GSIS) was assessed in 1h-static incubations and is expressed as mean of the percent of insulin content ± SEM. Significance was tested using a two-way ANOVA with post hoc adjustment for multiple comparisons. Results: RGS9 transcripts were detected in beta, alpha and delta cells in mouse pancreatic sections and both RGS9-1 and -2 isoforms were detected in whole islet extracts. RGS9 knockdown with two distinct shRNAs decreased KCl-stimulated insulin secretion (Control: 4.9±1.0 versus shRNA1: 1.3±0.3 p<0.0001 and shRNA2: 2.8±0.4 p<0.05, n=5-6). Surprisingly, in RGS9 knockout (RGS9Δexon2-4) islets GSIS was not affected (wild-type: 0.8±0.1 versus mutant: 0.7±0.06, n=6, ns). However, expression of alternative, truncated RGS9 transcripts were detected in RGS9Δexon2-4 islets, and GSIS was reduced upon RGS9 knockdown in RGS9Δexon2-4 islets (Control: 1.1±0.4 versus shRNA1: 0.3±0.1 p<0.01, n=4). Conclusion: RGS9 positively controls insulin secretion. Preserved GSIS in RGS9Δexon2-4 islets may be due to compensation from truncated RGS9. Disclosure S. Ferragne: None. S.A. Campbell: Employee; Applied Pharmaceutical Innovation, Hepion Pharmaceuticals. L. Reininger: None. C. Tremblay: None. J. Ghislain: None. V. Poitout: Research Support; Biodexa. Funding Natural Sciences and Engineering Research Council of CanadaFonds de recherche du Québec - Nature et technologie
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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) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.003 |
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".