ArticleCell reports2021
Sex-biased islet β cell dysfunction is caused by the MODY MAFA S64F variant by inducing premature aging and senescence in males.
Open access · goldAbstract readComparative Study
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Article in Cell reports, 2021. 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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34citing papers in PubMed
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34 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- Genetic background modulates MafADiabetologia · 2026Article
- Dual phenotype in a patient with adult-onset hyperinsulinism and diabetes caused by an activatingJournal of the Endocrine Society · 2026Article
- Developmental Control of DNA Damage Responses in α- and β-Cells Shapes the Selective β-Cell Susceptibility in Diabetes.Diabetes · 2026Article
- Article
- Review
- Pancreatic β-cell aging in physiology and diabetes: emerging roles of m6A mRNA methylation.Journal of molecular endocrinology · 2026Review
- Developmental control of DNA damage responses in α- and β-cells shapes the selective beta-cell susceptibility in diabetes.bioRxiv : the preprint server for biology · 2025Article
- Nucleolar stress facilitates islet β cell senescence via hijacking the DNA damage response pathways.iScience · 2025Article
- The role of the beta cell in type 2 diabetes: new findings from the last 5 years.Diabetologia · 2025Review
- Neuroendocrine Tumors: Germline Genetics and Hereditary Syndromes.Current treatment options in oncology · 2025Review
- SenNet recommendations for detecting senescent cells in different tissues.Nature reviews. Molecular cell biology · 2024Review
- Sex-specific regulatory architecture of pancreatic islets from subjects with and without type 2 diabetes.The EMBO journal · 2024Article
- Safeguarding genomic integrity in beta-cells: implications for beta-cell differentiation, growth, and dysfunction.Biochemical Society transactions · 2024Review
- Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice.Nature communications · 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
- 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
- Exploring senescence as a modifier of β cell extracellular vesicles in type 1 diabetes.Frontiers in endocrinology · 2024Review
- Stress-induced β cell early senescence confers protection against type 1 diabetes.Cell metabolism · 2023Article
- Exploring Large MAF Transcription Factors: Functions, Pathology, and Mouse Models with Point Mutations.Genes · 2023Review
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Authors and funding
13 authors at 5 institutions in 2 countries.
Emily M WalkerDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
Jeeyeon ChaDivision of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Xin TongDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
Min GuoDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
Jin-Hua LiuDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
Sophia YuDivision of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Donato IacovazzoCentre for Endocrinology, Barts and The London School of Medicine, Queen Mary University of London, London EC1M 6BQ, UK.
Franck Mauvais-JarvisSection of Endocrinology and Metabolism, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA; Southeast Louisiana Veterans Healthcare System, New Orleans, LA, USA; Tulane Center of Excellence in Sex-Based Biology & Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA.
Sarah E FlanaganInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter EX2 5DW, UK.
Márta KorbonitsCentre for Endocrinology, Barts and The London School of Medicine, Queen Mary University of London, London EC1M 6BQ, UK.
John StaffordDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Tennessee Valley Healthcare System, Veterans Affairs, Nashville, TN, USA.
David A JacobsonDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
Roland SteinDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA. Electronic address: roland.stein@vanderbilt.edu.
Vanderbilt University · USQueen Mary University of London · GBVanderbilt University Medical Center · USTulane University · USUniversity of Exeter · GB
Funding
Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8MTranslational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9MVanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALVIN C POWERS · 2012 to 2026
$29.3MRegional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3MShop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David J. Calkins · 1989 to 2026
$19.6MTHREE-TIERED PREVENTION MODEL TO BETTER SERVE ALL STUDENP30HD015052 · NICHD · VANDERBILT UNIVERSITY · PI HARRELL, FRANK E. · 1985 to 2014
$18.6MVanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9MTranslational Research in Endocrinology And Diabetes (TREAD)T32DK007061 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Sarah S Jaser, KEVIN D NISWENDER · 1986 to 2026
$8.0MResearch Project: Sensory and Multisensory Contributions to AutismU54HD083211 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DYKENS, ELISABETH MAY · 2015 to 2019
$7.1MTargeting the estrogen receptor-α to protect functional β-cell mass in womenR01DK074970 · NIDDK · TULANE UNIVERSITY OF LOUISIANA · PI Franck Mauvais-Jarvis · 2007 to 2026
$6.0MDefining the Role of MafA in Islet Beta CellsR01DK090570 · NIDDK · VANDERBILT UNIVERSITY · PI PARENT, AUDREY, STEIN, ROLAND W · 2011 to 2025
$5.9MSex-Specific Risk of Metabolic and Cardiovascular DiseaseR01HL144846 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI John Michael Stafford · 2019 to 2026
$4.1MBLRD VA I01 BX003725Diabetes UK 16/0005395Doris Duke Charitable Foundation 2020063NCI NIH HHS P30 CA068485NEI NIH HHS P30 EY008126NHLBI NIH HHS R01 HL144846NICHD NIH HHS P30 HD015052NICHD NIH HHS U54 HD083211NIDDK NIH HHS F32 DK109577NIDDK NIH HHS K01 DK133533NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK074970NIDDK NIH HHS R01 DK090570NIDDK NIH HHS R01 DK097392NIDDK NIH HHS R01 DK107444NIDDK NIH HHS R01 DK109102NIDDK NIH HHS R01 DK115620NIDDK NIH HHS T32 DK007061NIDDK NIH HHS U24 DK059637Wellcome TrustWellcome Trust 105636/Z/14/Z
Abstract
A heterozygous missense mutation of the islet β cell-enriched MAFA transcription factor (p.Ser64Phe [S64F]) is found in patients with adult-onset β cell dysfunction (diabetes or insulinomatosis), with men more prone to diabetes than women. This mutation engenders increased stability to the unstable MAFA protein. Here, we develop a S64F MafA mouse model to determine how β cell function is affected and find sex-dependent phenotypes. Heterozygous mutant males (MafA
Indexed as
Cellular SenescenceAnimalsAnimals, Genetically ModifiedBlood GlucoseCalcium SignalingCell LineDiabetes Mellitus, Type 2Disease Models, AnimalDNA DamageFemaleGenetic Predisposition to DiseaseHumansInsulinInsulin-Secreting CellsMaf Transcription Factors, LargeMaleBlood GlucoseInsulinMAFA protein, humanMafa protein, mouseMaf Transcription Factors, Largebeta cellcellular senescencediabetesislet biologyMAFAsexual dimorphism
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