ArticleProceedings of the National Academy of Sciences of the United States of America2015
Gαi/o-coupled receptor signaling restricts pancreatic β-cell expansion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 69 citations in OpenAlex.
- The Role of G Protein-Coupled Receptors and Receptor Kinases in PancreaticPharmacological reviews · 2024Review
- The adhesion GPCR GPR116/ADGRF5 has a dual function in pancreatic islets regulating somatostatin release and islet development.Communications biology · 2024Article
- Glucose-stimulated insulin secretion depends on FFA1 and Gq in neonatal mouse islets.Diabetologia · 2023Article
- G Protein-Coupled Receptors and the Rise of Type 2 Diabetes in Children.Biomedicines · 2023Review
- MafB-dependent neurotransmitter signaling promotes β cell migration in the developing pancreas.Development (Cambridge, England) · 2023Article
- Hyperaminoacidemia induces pancreatic α cell proliferation via synergism between the mTORC1 and CaSR-Gq signaling pathways.Nature communications · 2023Article
- Therapeutic Strategies Targeting Pancreatic Islet β-Cell Proliferation, Regeneration, and Replacement.Endocrinology · 2022Article
- GNature communications · 2022Article
- Dual pancreatic adrenergic and dopaminergic signaling as a therapeutic target of bromocriptine.iScience · 2022Article
- In Vivo Metabolic Roles of G Proteins of the Gi Family Studied With Novel Mouse Models.Endocrinology · 2022Review
- Gsα-dependent signaling is required for postnatal establishment of a functional β-cell mass.Molecular metabolism · 2021Article
- Stage-specific transcriptomic changes in pancreatic α-cells after massive β-cell loss.BMC genomics · 2021Article
- Silencing the G-protein coupled receptor 3-salt inducible kinase 2 pathway promotes human β cell proliferation.Communications biology · 2021Article
- Article
- Paracrine signaling in islet function and survival.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Free fatty acid receptor 3 differentially contributes to β-cell compensation under high-fat diet and streptozotocin stress.American journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- GPCRs show widespread differential mRNA expression and frequent mutation and copy number variation in solid tumors.PLoS biology · 2019Article
- The autonomic nervous system regulates pancreatic β-cell proliferation in adult male rats.American journal of physiology. Endocrinology and metabolism · 2019Article
- Adrb2 controls glucose homeostasis by developmental regulation of pancreatic islet vasculature.eLife · 2018Article
- The somatostatin-secreting pancreatic δ-cell in health and disease.Nature reviews. Endocrinology · 2018Review
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Gi-GPCRs, G protein-coupled receptors that signal via Gα proteins of the i/o class (Gαi/o), acutely regulate cellular behaviors widely in mammalian tissues, but their impact on the development and growth of these tissues is less clear. For example, Gi-GPCRs acutely regulate insulin release from pancreatic β cells, and variants in genes encoding several Gi-GPCRs--including the α-2a adrenergic receptor, ADRA2A--increase the risk of type 2 diabetes mellitus. However, type 2 diabetes also is associated with reduced total β-cell mass, and the role of Gi-GPCRs in establishing β-cell mass is unknown. Therefore, we asked whether Gi-GPCR signaling regulates β-cell mass. Here we show that Gi-GPCRs limit the proliferation of the insulin-producing pancreatic β cells and especially their expansion during the critical perinatal period. Increased Gi-GPCR activity in perinatal β cells decreased β-cell proliferation, reduced adult β-cell mass, and impaired glucose homeostasis. In contrast, Gi-GPCR inhibition enhanced perinatal β-cell proliferation, increased adult β-cell mass, and improved glucose homeostasis. Transcriptome analysis detected the expression of multiple Gi-GPCRs in developing and adult β cells, and gene-deletion experiments identified ADRA2A as a key Gi-GPCR regulator of β-cell replication. These studies link Gi-GPCR signaling to β-cell mass and diabetes risk and identify it as a potential target for therapies to protect and increase β-cell mass in patients with diabetes.
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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.