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  • Rönn, TinaLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital (author)

Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • Springer Nature,2023
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-218632
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-218632URI
  • https://doi.org/10.1038/s41467-023-43719-9DOI
  • https://lup.lub.lu.se/record/4bfc32c6-4ec8-4bcd-bf57-f66db28f2085URI

Supplementary language notes

  • Language:English
  • Summary in:English

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Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Epigenetic dysregulation may influence disease progression. Here we explore whether epigenetic alterations in human pancreatic islets impact insulin secretion and type 2 diabetes (T2D). In islets, 5,584 DNA methylation sites exhibit alterations in T2D cases versus controls and are associated with HbA1c in individuals not diagnosed with T2D. T2D-associated methylation changes are found in enhancers and regions bound by β-cell-specific transcription factors and associated with reduced expression of e.g. CABLES1, FOXP1, GABRA2, GLR1A, RHOT1, and TBC1D4. We find RHOT1 (MIRO1) to be a key regulator of insulin secretion in human islets. Rhot1-deficiency in β-cells leads to reduced insulin secretion, ATP/ADP ratio, mitochondrial mass, Ca2+, and respiration. Regulators of mitochondrial dynamics and metabolites, including L-proline, glycine, GABA, and carnitines, are altered in Rhot1-deficient β-cells. Islets from diabetic GK rats present Rhot1-deficiency. Finally, RHOT1methylation in blood is associated with future T2D. Together, individuals with T2D exhibit epigenetic alterations linked to mitochondrial dysfunction in pancreatic islets.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Ofori, Jones K.Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-joi (author)
  • Perfilyev, AlexanderLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-apy (author)
  • Hamilton, AlexanderLund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,University of Copenhagen,Skåne University Hospital(Swepub:lu)al1346ha (author)
  • Pircs, KarolinaLund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Molecular Neurogenetics,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Semmelweis University(Swepub:lu)med-kpc (author)
  • Eichelmann, FabianDepartment of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research, München-Neuherberg, Germany (author)
  • Garcia-Calzon, SoniaLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,University of Navarra,Skåne University Hospital(Swepub:lu)med-sg_ (author)
  • Karagiannopoulos, AlexandrosLund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,Skåne University Hospital(Swepub:lu)al6183ka (author)
  • Stenlund, HansUmeå University,Umeå universitet(Swepub:umu)hasstd97 (author)
  • Wendt, AnnaLund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-awe (author)
  • Volkov, PetrLund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-pvo (author)
  • Schulze, Matthias B.Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research, München-Neuherberg, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany (author)
  • Mulder, HindrikLund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medk-hmu (author)
  • Eliasson, LenaLund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-lel (author)
  • Ruhrmann, SabrinaLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital(Swepub:lu)sa4447ru (author)
  • Bacos, KarlLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medk-kb0 (author)
  • Ling, CharlotteLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital(Swepub:lu)endo-cl0 (author)
  • Diabetes - epigenetikForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:Nature Communications: Springer Nature14:12041-1723

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