ArticleProceedings of the National Academy of Sciences of the United States of America2010
Extranuclear estrogen receptor-alpha stimulates NeuroD1 binding to the insulin promoter and favors insulin synthesis.
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 80 papers.
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Who cites it
80 citing papers in PubMed, 136 citations in OpenAlex.
- Sex-specific systemic and brain metabolic responses to a standardized ketogenic diet in mice.Lab animal · 2026Article
- FOXM1 cooperates with ERα to regulate functional β-cell mass.American journal of physiology. Endocrinology and metabolism · 2025Article
- Sex-specific regulatory architecture of pancreatic islets from subjects with and without type 2 diabetes.The EMBO journal · 2024Article
- Metabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations.The Journal of clinical investigation · 2024Review
- Review
- Single cell regulatory architecture of human pancreatic islets suggests sex differences in β cell function and the pathogenesis of type 2 diabetes.Research square · 2024Article
- Spaceflight induces changes in gene expression profiles linked to insulin and estrogen.Communications biology · 2024Article
- Single cell regulatory architecture of human pancreatic islets suggests sex differences in β cell function and the pathogenesis of type 2 diabetes.bioRxiv : the preprint server for biology · 2024Article
- Follicle-stimulating hormone orchestrates glucose-stimulated insulin secretion of pancreatic islets.Nature communications · 2023Article
- Decoding pancreatic endocrine cell differentiation and β cell regeneration in zebrafish.Science advances · 2023Article
- The potent contraceptive gestodene exerts insulinotropic effects through its a-ring reduced metabolites with intrinsic estrogen-like activity in pancreatic β-cells.Journal of endocrinological investigation · 2023Article
- Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells.Cell reports · 2023Article
- Chromosomal and gonadal factors regulate microglial sex effects in the aging brain.Brain research bulletin · 2023Review
- Role of estrogen in the regulation of central and peripheral energy homeostasis: from a menopausal perspective.Therapeutic advances in endocrinology and metabolism · 2023Review
- Membrane estrogen receptor-α contributes to female protection against high-fat diet-induced metabolic disorders.Frontiers in endocrinology · 2023Article
- Membrane-Initiated Estrogen, Androgen, and Progesterone Receptor Signaling in Health and Disease.Endocrine reviews · 2022Review
- Efficacy of glucagon-like peptide-1 and estrogen dual agonist in pancreatic islets protection and pre-clinical models of insulin-deficient diabetes.Cell reports. Medicine · 2022Article
- Dual Beneficial Effects of α-Spinasterol Isolated fromPlants (Basel, Switzerland) · 2022Article
- Adapting Physiology in Functional Human Islet Organogenesis.Frontiers in cell and developmental biology · 2022Article
- Beta-Cell Adaptation to Pregnancy - Role of Calcium Dynamics.Frontiers in endocrinology · 2022Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Estrogen receptors (ERs) protect pancreatic islet survival in mice through rapid extranuclear actions. ERalpha also enhances insulin synthesis in cultured islets. Whether ERalpha stimulates insulin synthesis in vivo and, if so, through which mechanism(s) remain largely unknown. To address these issues, we generated a pancreas-specific ERalpha knockout mouse (PERalpha KO(-/-)) using the Cre-loxP strategy and used a combination of genetic and pharmacologic tools in cultured islets and beta cells. Whereas 17beta-estradiol (E2) treatment up-regulates pancreatic insulin gene and protein content in control ERalpha lox/lox mice, these E2 effects are abolished in PERalpha KO(-/-) mice. We find that E2-activated ERalpha increases insulin synthesis by enhancing glucose stimulation of the insulin promoter activity. Using a knock-in mouse with a mutated ERalpha eliminating binding to the estrogen response elements (EREs), we show that E2 stimulation of insulin synthesis is independent of the ERE. We find that the extranuclear ERalpha interacts with the tyrosine kinase Src, which activates extracellular signal-regulated kinases(1/2), to increase nuclear localization and binding to the insulin promoter of the transcription factor NeuroD1. This study supports the importance of ERalpha in beta cells as a regulator of insulin synthesis in vivo.
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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.