ArticleProceedings of the National Academy of Sciences of the United States of America2010
RGS4 is a negative regulator of insulin release from pancreatic beta-cells in vitro and in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 94 citations in OpenAlex.
- Selective modulation of murine intestinal MAmerican journal of physiology. Cell physiology · 2026Article
- Maternal DNA methylation signatures of gestational diabetes across all stages of pregnancy.Journal of translational medicine · 2025Article
- Article
- The Regulator of G Protein Signaling 14 Knockout Mouse, a Model of Healthful Longevity Protects Against Obesity and Glucose Intolerance Through a Brown Adipose Tissue Mechanism.International journal of molecular sciences · 2025Article
- Regulator of G protein signaling protein 6 alleviates acute lung injury by inhibiting inflammation and promoting cell self-renewal in mice.Cellular & molecular biology letters · 2023Article
- The Potential Role of R4 Regulators of G Protein Signaling (RGS) Proteins in Type 2 Diabetes Mellitus.Cells · 2022Review
- Oscillatory calcium release and sustained store-operated oscillatory calcium signaling prevents differentiation of human oligodendrocyte progenitor cells.Scientific reports · 2022Article
- RGS4-Deficiency Alters Intracellular Calcium and PKA-Mediated Control of Insulin Secretion in Glucose-Stimulated Beta Islets.Biomedicines · 2021Article
- β-Arrestin-1 is required for adaptive β-cell mass expansion during obesity.Nature communications · 2021Article
- Single Molecule-Based fliFISH Validates Radial and Heterogeneous Gene Expression Patterns in Pancreatic Islet β-Cells.Diabetes · 2021Article
- The association between RGS4 and choline in cardiac fibrosis.Cell communication and signaling : CCS · 2021Article
- Identification of hub genes related to the progression of type 1 diabetes by computational analysis.BMC endocrine disorders · 2021Article
- Article
- PDX1Nature communications · 2021Article
- SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β cells.Scientific reports · 2020Article
- The regulatory G protein signaling complex, Gβ5-R7, promotes glucose- and extracellular signal-stimulated insulin secretion.The Journal of biological chemistry · 2020Article
- Targeting RGS4 Ablates Glioblastoma Proliferation.International journal of molecular sciences · 2020Article
- GPCRs, G Proteins, and Their Impact on β-cell Function.Comprehensive Physiology · 2020Review
- Allosteric modulation of β-cell MProceedings of the National Academy of Sciences of the United States of America · 2019Article
- β-Cell-intrinsic β-arrestin 1 signaling enhances sulfonylurea-induced insulin secretion.The Journal of clinical investigation · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Therapeutic strategies that augment insulin release from pancreatic beta-cells are considered beneficial in the treatment of type 2 diabetes. We previously demonstrated that activation of beta-cell M(3) muscarinic receptors (M3Rs) greatly promotes glucose-stimulated insulin secretion (GSIS), suggesting that strategies aimed at enhancing signaling through beta-cell M3Rs may become therapeutically useful. M3R activation leads to the stimulation of G proteins of the G(q) family, which are under the inhibitory control of proteins known as regulators of G protein signaling (RGS proteins). At present, it remains unknown whether RGS proteins play a role in regulating insulin release. To address this issue, we initially demonstrated that MIN6 insulinoma cells express functional M3Rs and that RGS4 was by far the most abundant RGS protein expressed by these cells. Strikingly, siRNA-mediated knockdown of RGS4 expression in MIN6 cells greatly enhanced M3R-mediated augmentation of GSIS and calcium release. We obtained similar findings using pancreatic islets prepared from RGS4-deficient mice. Interestingly, RGS4 deficiency had little effect on insulin release caused by activation of other beta-cell GPCRs. Finally, treatment of mutant mice selectively lacking RGS4 in pancreatic beta-cells with a muscarinic agonist (bethanechol) led to significantly increased plasma insulin and reduced blood glucose levels, as compared to control littermates. Studies with beta-cell-specific M3R knockout mice showed that these responses were mediated by beta-cell M3Rs. These findings indicate that RGS4 is a potent negative regulator of M3R function in pancreatic beta-cells, suggesting that RGS4 may represent a potential target to promote insulin release for therapeutic purposes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.