ArticlePLoS genetics2012
An siRNA screen in pancreatic beta cells reveals a role for Gpr27 in insulin production.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
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- Spatial and quantitative gene expression analysis of SREB receptors in the gonads of green-spotted pufferfish (Dichotomyctere nigroviridis).General and comparative endocrinology · 2025Article
- RNA therapeutics in targeting G protein-coupled receptors: Recent advances and challenges.Molecular therapy. Nucleic acids · 2024Review
- Stimulation of insulin secretion induced by low 4-cresol dose involves the RPS6KA3 signalling pathway.PloS one · 2024Article
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- Characterizing the SREB G protein-coupled receptor family in fish: Brain gene expression and genomic differences in upstream transcription factor binding sites.Comparative biochemistry and physiology. Part A, Molecular & integrative physiology · 2023Article
- A Superfolder Green Fluorescent Protein-Based Biosensor Allows Monitoring of Chloride in the Endoplasmic Reticulum.ACS sensors · 2022Article
- Phoenixin-14 alters transcriptome and steroid profiles in female green-spotted puffer (Dichotomyctere nigroviridis).Scientific reports · 2022Article
- The Activation of GPR27 Increases Cytosolic L-Lactate in 3T3 Embryonic Cells and Astrocytes.Cells · 2022Article
- Large-Scale Functional Genomics Screen to Identify Modulators of Human β-Cell Insulin Secretion.Biomedicines · 2022Article
- Stem Cell-Derived β Cells: A Versatile Research Platform to Interrogate the Genetic Basis of β Cell Dysfunction.International journal of molecular sciences · 2022Review
- GPR27 Regulates Hepatocellular Carcinoma Progression via MAPK/ERK Pathway.Cancer management and research · 2022Article
- Silencing the G-protein coupled receptor 3-salt inducible kinase 2 pathway promotes human β cell proliferation.Communications biology · 2021Article
- Characterization of the G protein-coupled receptor family SREB across fish evolution.Scientific reports · 2021Article
- Sept8/SEPTIN8 involvement in cellular structure and kidney damage is identified by genetic mapping and a novel human tubule hypoxic model.Scientific reports · 2021Article
- Which Hyperglycemic Model of Zebrafish (Frontiers in cell and developmental biology · 2021Review
- Deletion of Gpr27 in vivo reduces insulin mRNA but does not result in diabetes.Scientific reports · 2020Article
- Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Epigenetic regulation of motivated behaviors by histone deacetylase inhibitors.Neuroscience and biobehavioral reviews · 2019Review
- New α- and SIN γ-retrovectors for safe transduction and specific transgene expression in pancreatic β cell lines.BMC biotechnology · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The prevalence of type 2 diabetes in the United States is projected to double or triple by 2050. We reasoned that the genes that modulate insulin production might be new targets for diabetes therapeutics. Therefore, we developed an siRNA screening system to identify genes important for the activity of the insulin promoter in beta cells. We created a subclone of the MIN6 mouse pancreatic beta cell line that expresses destabilized GFP under the control of a 362 base pair fragment of the human insulin promoter and the mCherry red fluorescent protein under the control of the constitutively active rous sarcoma virus promoter. The ratio of the GFP to mCherry fluorescence of a cell indicates its insulin promoter activity. As G protein coupled receptors (GPCRs) have emerged as novel targets for diabetes therapies, we used this cell line to screen an siRNA library targeting all known mouse GPCRs. We identified several known GPCR regulators of insulin secretion as regulators of the insulin promoter. One of the top positive regulators was Gpr27, an orphan GPCR with no known role in beta cell function. We show that knockdown of Gpr27 reduces endogenous mouse insulin promoter activity and glucose stimulated insulin secretion. Furthermore, we show that Pdx1 is important for Gpr27's effect on the insulin promoter and insulin secretion. Finally, the over-expression of Gpr27 in 293T cells increases inositol phosphate levels, while knockdown of Gpr27 in MIN6 cells reduces inositol phosphate levels, suggesting this orphan GPCR might couple to Gq/11. In summary, we demonstrate a MIN6-based siRNA screening system that allows rapid identification of novel positive and negative regulators of the insulin promoter. Using this system, we identify Gpr27 as a positive regulator of insulin production.
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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.