ArticleCell reports2018
Estrogens Promote Misfolded Proinsulin Degradation to Protect Insulin Production and Delay Diabetes.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 86 citations in OpenAlex.
- Efficacy of postmenopausal estrogen replacement in SIV-infected female macaques on antiretroviral therapy.bioRxiv : the preprint server for biology · 2026Article
- Age at Menopause and Trajectories of Multimorbidity Progression to Mortality: A Multi-State Analysis of UK Biobank Data.BJOG : an international journal of obstetrics and gynaecology · 2026Article
- Article
- Sex Differences in ER Stress Pathways Are a Key Determinant of β-Cell Proliferation and Resilience.Diabetes · 2026Article
- Biological sex affects human islet gene expression and mitochondrial function in type 2 diabetes.Endocrinology · 2026Article
- Limiting ER-associated degradation capacity triggers acute and chronic effects on insulin biosynthesis.The Journal of clinical investigation · 2026Article
- Intrinsic muscle stem cell dysfunction underlies functional deficits in models of type 1 diabetes.NPJ Regenerative medicine · 2026Article
- Sex hormones and functional gastrointestinal disorders in menopausal women.Frontiers in endocrinology · 2026Review
- Metabolic Messengers: testosterone.Nature metabolism · 2026Review
- TLR4 deletion reduces small fiber sensory abnormalities and nerve degeneration in diabetic male mice.Neuroscience · 2025Article
- Biological sex affects human islet gene expression and mitochondrial function in type 2 diabetes.bioRxiv : the preprint server for biology · 2025Article
- Renalase inhibition defends against acute and chronic β cell stress by regulating cell metabolism.Molecular metabolism · 2025Article
- The role of estrogen in the sex difference for the risk factors of heart failure with preserved ejection fraction.Biology direct · 2025Review
- Exploring proinsulin proteostasis: insights into beta cell health and diabetes.Frontiers in molecular biosciences · 2025Review
- Deciphering the role of classical oestrogen receptor in insulin resistance and type 2 diabetes mellitus: From molecular mechanism to clinical evidence.BioImpacts : BI · 2025Review
- Sex-specific regulatory architecture of pancreatic islets from subjects with and without type 2 diabetes.The EMBO journal · 2024Article
- miR-10a/b-5p-NCOR2 Regulates Insulin-Resistant Diabetes in Female Mice.International journal of molecular sciences · 2024Article
- Metabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations.The Journal of clinical investigation · 2024Review
- Effect of Postmenopausal Hormone Therapy on Metabolic Syndrome and Its Components.Journal of clinical medicine · 2024Article
- 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
1 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
Conjugated estrogens (CE) delay the onset of type 2 diabetes (T2D) in postmenopausal women, but the mechanism is unclear. In T2D, the endoplasmic reticulum (ER) fails to promote proinsulin folding and, in failing to do so, promotes ER stress and β cell dysfunction. We show that CE prevent insulin-deficient diabetes in male and in female Akita mice using a model of misfolded proinsulin. CE stabilize the ER-associated protein degradation (ERAD) system and promote misfolded proinsulin proteasomal degradation. This involves activation of nuclear and membrane estrogen receptor-α (ERα), promoting transcriptional repression and proteasomal degradation of the ubiquitin-conjugating enzyme and ERAD degrader, UBC6e. The selective ERα modulator bazedoxifene mimics CE protection of β cells in females but not in males.
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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.