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Type 2 diabetes can...
Type 2 diabetes candidate genes, including PAX5, cause impaired insulin secretion in human pancreatic islets
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- Bacos, Karl (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital
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- Perfilyev, Alexander (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital
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- Karagiannopoulos, Alexandros (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Skåne University Hospital
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- Cowan, Elaine (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Skåne University Hospital
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- Ofori, Jones K (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital
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- Bertonnier-Brouty, Ludivine (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Endokrin Celldifferentiering,Forskargrupper vid Lunds universitet,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Endocrine Cell Differentiation and Function,Lund University Research Groups
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- Rönn, Tina (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital
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- Lindqvist, Andreas (author)
- Lund University,Lunds universitet,Neuroendokrin cellbiologi,Forskargrupper vid Lunds universitet,Neuroendocrine Cell Biology,Lund University Research Groups
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- Luan, Cheng (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Ruhrmann, Sabrina (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital
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- Ngara, Mtakai (author)
- Karolinska Institutet,Lund University,Lunds universitet,Neuroendokrin cellbiologi,Forskargrupper vid Lunds universitet,Neuroendocrine Cell Biology,Lund University Research Groups
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- Nilsson, Åsa (author)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,Skåne University Hospital
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- Gheibi, Sevda (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups,Skåne University Hospital
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- Lyons, Claire L (author)
- Lund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Diabetes - molekylär metabolism,Medical Protein Science,Lund University Research Groups,Diabetes - Molecular Metabolism,Skåne University Hospital
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- Lagerstedt, Jens O (author)
- Lund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Medical Protein Science,Lund University Research Groups,Skåne University Hospital
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- Barghouth, Mohammad (author)
- Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
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- Esguerra, Jonathan Ls (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Skåne University Hospital
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- Volkov, Petr (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups
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- Fex, Malin (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups,Skåne University Hospital
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- Mulder, Hindrik (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups,Skåne University Hospital
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- Wierup, Nils (author)
- Lund University,Lunds universitet,Neuroendokrin cellbiologi,Forskargrupper vid Lunds universitet,Neuroendocrine Cell Biology,Lund University Research Groups
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- Krus, Ulrika (author)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,Skåne University Hospital
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- Artner, Isabella (author)
- Lund University,Lunds universitet,Endokrin Celldifferentiering,Forskargrupper vid Lunds universitet,Bildbehandlingsplattformen,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Endocrine Cell Differentiation and Function,Lund University Research Groups,Imaging,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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- Eliasson, Lena (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Skåne University Hospital
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- Prasad, Rashmi B (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki,Skåne University Hospital
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- Cataldo, Luis Rodrigo (author)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups,University of Copenhagen,Skåne University Hospital
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- Ling, Charlotte (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: The Journal of clinical investigation. - 0021-9738 .- 1558-8238. ; 133:4
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Abstract
Subject headings
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- Type 2 diabetes (T2D) is caused by insufficient insulin secretion from pancreatic β-cells. To identify candidates contributing to T2D pathophysiology, we studied human pancreatic islets from ~300 individuals. We found 395 differentially expressed genes (DEGs) in islets from individuals with T2D, including, to our knowledge, novel (OPRD1, PAX5, TET1) and previously identified (CHL1, GLRA1, IAPP) candidates. A third of the identified islet expression changes may predispose to diabetes, as they associated with HbA1c in individuals not previously diagnosed with T2D. Most DEGs were expressed in human β-cells based on single-cell RNA-sequencing data. Additionally, DEGs displayed alterations in open chromatin and associated with T2D-SNPs. Mouse knock-out strains demonstrated that T2D-associated candidates regulate glucose homeostasis and body composition in vivo. Functional validation showed that mimicking T2D-associated changes for OPRD1, PAX5, and SLC2A2 impaired insulin secretion. Impairments in Pax5-overexpressing β-cells were due to severe mitochondrial dysfunction. Finally, we discovered PAX5 as a potential transcriptional regulator of many T2D-associated DEGs in human islets. Overall, we identified molecular alterations in human pancreatic islets contributing to β-cell dysfunction in T2D pathophysiology.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Bacos, Karl
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Perfilyev, Alexa ...
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Karagiannopoulos ...
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Cowan, Elaine
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Ofori, Jones K
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Bertonnier-Brout ...
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show more...
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Rönn, Tina
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Lindqvist, Andre ...
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Luan, Cheng
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Ruhrmann, Sabrin ...
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Ngara, Mtakai
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Nilsson, Åsa
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Gheibi, Sevda
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Lyons, Claire L
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Lagerstedt, Jens ...
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Barghouth, Moham ...
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Esguerra, Jonath ...
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Volkov, Petr
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Fex, Malin
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Mulder, Hindrik
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Wierup, Nils
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Krus, Ulrika
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Artner, Isabella
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Eliasson, Lena
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Prasad, Rashmi B
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Cataldo, Luis Ro ...
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Ling, Charlotte
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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The Journal of c ...
- By the university
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Lund University
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Karolinska Institutet