ArticleCell reports2017
Fumarate Hydratase Deletion in Pancreatic β Cells Leads to Progressive Diabetes.
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Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41citing papers in PubMed
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41 citing papers in PubMed, 63 citations in OpenAlex.
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- Glutamate accumulation in myelofibrosis microenvironment rewires mesenchymal stromal cells metabolic and epigenetic profiles.Cell communication and signaling : CCS · 2026Article
- Impaired glucose tolerance and mild diabetes induce β-cell dysfunction in mice.Nature communications · 2026Article
- Article
- Fumarate hydratase ameliorates pressure overload induced cardiac remodeling by controlling Elovl7-mediated biosynthesis of unsaturated fatty acids.Acta pharmacologica Sinica · 2026Article
- Metabolomic Insights Into the Impact of a Maternal Western-Style Diet and Leptin Supplementation During Suckling on Adult Rat Offspring.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells.Genes & development · 2025Article
- Insulin receptor isoform B is required for efficient proinsulin processing in pancreatic β cells.iScience · 2024Article
- TALK-1-mediated alterations of β-cell mitochondrial function and insulin secretion impair glucose homeostasis on a diabetogenic diet.Cell reports · 2024Article
- FH Variant Pathogenicity Promotes Purine Salvage Pathway Dependence in Kidney Cancer.Cancer discovery · 2023Article
- Circulating succinate-modifying metabolites accurately classify and reflect the status of fumarate hydratase-deficient renal cell carcinoma.The Journal of clinical investigation · 2023Article
- Review
- Pharmacologic inhibition of somatostatin receptor 2 to restore glucagon counterregulation in diabetes.Frontiers in pharmacology · 2023Review
- Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells.Nature communications · 2022Article
- Kinetic and data-driven modeling of pancreatic β-cell central carbon metabolism and insulin secretion.PLoS computational biology · 2022Article
- Reduced expression of mitochondrial fumarate hydratase in progressive multiple sclerosis contributes to impaired in vitro mesenchymal stromal cell-mediated neuroprotection.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Article
- β-Cell Succinate Dehydrogenase Deficiency Triggers Metabolic Dysfunction and Insulinopenic Diabetes.Diabetes · 2022Article
- Bezafibrate Reduces Elevated Hepatic Fumarate in Insulin-Deficient Mice.Biomedicines · 2022Article
- Effects of first-line diabetes therapy with biguanides, sulphonylurea and thiazolidinediones on the differentiation, proliferation and apoptosis of islet cell populations.Journal of endocrinological investigation · 2022Article
- The Molecular Role of HIF1α Is Elucidated in Chronic Myeloid Leukemia.Frontiers in oncology · 2022Article
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Authors and funding
28 authors at 10 institutions in 6 countries.
Julie AdamRadcliffe Department of Medicine, OCDEM, Churchill Hospital, University of Oxford, Oxford OX3 7LE, UK; Nuffield Department of Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, UK; Nuffield Department of Medicine, NDMRB, University of Oxford, Oxford OX3 7FZ, UK. Electronic address: julie.adam@ndm.ox.ac.uk.
Reshma RamracheyaRadcliffe Department of Medicine, OCDEM, Churchill Hospital, University of Oxford, Oxford OX3 7LE, UK.
Margarita V ChibalinaRadcliffe Department of Medicine, OCDEM, Churchill Hospital, University of Oxford, Oxford OX3 7LE, UK.
Nicola TernetteThe Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
Alexander HamiltonRadcliffe Department of Medicine, OCDEM, Churchill Hospital, University of Oxford, Oxford OX3 7LE, UK.
Andrei I TarasovRadcliffe Department of Medicine, OCDEM, Churchill Hospital, University of Oxford, Oxford OX3 7LE, UK.
Quan ZhangRadcliffe Department of Medicine, OCDEM, Churchill Hospital, University of Oxford, Oxford OX3 7LE, UK.
Eduardo RebelatoRadcliffe Department of Medicine, OCDEM, Churchill Hospital, University of Oxford, Oxford OX3 7LE, UK; Department of Biophysics, Federal University of Sao Paulo, Sao Paulo 04023-062, Brazil.
Nils J G RorsmanRadcliffe Department of Medicine, OCDEM, Churchill Hospital, University of Oxford, Oxford OX3 7LE, UK.
Rafael Martín-Del-RíoInstituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Ramón y Cajal Hospital, Madrid, Spain.
Amy LewisCentre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Gizem ÖzkanNuffield Department of Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, UK.
Hyun Woong DoRadcliffe Department of Medicine, OCDEM, Churchill Hospital, University of Oxford, Oxford OX3 7LE, UK.
Peter SpégelCentre for Analysis and Synthesis, Department of Chemistry, Lund University, Box 124, 221 00 Lund, Sweden.
Kaori SaitohInstitute for Advanced Biosciences, Keio University, 246-2 Mizukami, Tsuruoka, Yamagata 997-0052, Japan.
Keiko KatoInstitute for Advanced Biosciences, Keio University, 246-2 Mizukami, Tsuruoka, Yamagata 997-0052, Japan.
Kaori IgarashiInstitute for Advanced Biosciences, Keio University, 246-2 Mizukami, Tsuruoka, Yamagata 997-0052, Japan.
Benedikt M KesslerTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
Christopher W PughNuffield Department of Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, UK; Nuffield Department of Medicine, NDMRB, University of Oxford, Oxford OX3 7FZ, UK.
Jorge Tamarit-RodriguezBiochemistry Department, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
Hindrik MulderLund University Diabetes Centre, Unit of Molecular Metabolism, Clinical Research Centre, Malmo University Hospital, 20502 Malmo, Sweden.
Anne ClarkRadcliffe Department of Medicine, OCDEM, Churchill Hospital, University of Oxford, Oxford OX3 7LE, UK.
Norma FrizzellDepartment of Pharmacology, Physiology & Neuroscience, School of Medicine, University of South Carolina, Columbia, SC 29208, USA.
Tomoyoshi SogaInstitute for Advanced Biosciences, Keio University, 246-2 Mizukami, Tsuruoka, Yamagata 997-0052, Japan.
Frances M AshcroftDepartment of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK.
Andrew SilverCentre for Genomics and Child Health, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Patrick J PollardNuffield Department of Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN, UK; Department of Physiology, Institute of Neuroscience and Physiology, University of Göteborg, 405 30 Göteborg, Sweden.
Patrik RorsmanRadcliffe Department of Medicine, OCDEM, Churchill Hospital, University of Oxford, Oxford OX3 7LE, UK; Department of Physiology, Institute of Neuroscience and Physiology, University of Göteborg, 405 30 Göteborg, Sweden. Electronic address: patrik.rorsman@hmc.ox.ac.uk.
University of Oxford · GBChurchill Hospital · GBKeio University · JPLund University · SEQueen Mary University of London · GBInstituto Ramón y Cajal de Investigación Sanitaria · ESOxford Centre for Diabetes, Endocrinology and Metabolism · GBUniversidad Complutense de Madrid · ESUniversity of Gothenburg · SEUniversity of South Carolina · US
Funding
Medical Research Council G0801995Wellcome Trust 089795Wellcome Trust 095531/Z/11/Z
Abstract
We explored the role of the Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 in pancreatic β cells (Fh1βKO mice) appear normal for 6-8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1α or Nrf2. Progressive hyperglycemia in Fh1βKO mice led to dysregulated metabolism in β cells, a decrease in glucose-induced ATP production, electrical activity, cytoplasmic [Ca
Indexed as
AnimalsDiabetes Mellitus, Type 2Fumarate HydrataseHumansInsulin-Secreting CellsIslets of LangerhansMiceFumarate Hydratasediabetesfumaratefumarate hydrataseglucose metabolismhyperglycemiainsulinmouse modelpHsuccinationβ cell
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