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Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes

Axelsson, Annika (author)
University of Gothenburg,Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups,Diabetes - öcellsexocytos,Diabetes - Islet Cell Exocytosis,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,Sage Bionetworks
Mahdi, T (author)
Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups,Hawler Medical University
Nenonen, H. A. (author)
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Singh, Tania (author)
Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
Hänzelmann, S (author)
RWTH Aachen University
Wendt, A. (author)
Bagge, Annika (author)
Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
Reinbothe, T. M. (author)
Millstein, J. (author)
Sage Bionetworks
Yang, X (author)
Sage Bionetworks,University of California, Los Angeles
Zhang, B. (author)
Sage Bionetworks,Icahn School of Medicine at Mount Sinai
Gusmao, E. G. (author)
RWTH Aachen University
Shu, L. (author)
University of California, Los Angeles
Szabat, M. (author)
University of British Columbia
Tang, Y (author)
Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups,Tianjin Medical University
Wang, Jinling (author)
Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups,Xiamen University
Salö, S. (author)
Lund University
Eliasson, L (author)
Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
Artner, I (author)
Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
Fex, M (author)
Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Diabetes - molekylär metabolism,Celiac Disease and Diabetes Unit,Lund University Research Groups,Diabetes - Molecular Metabolism
Johnson, J D (author)
University of British Columbia
Wollheim, C B (author)
Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,University Medical Center, Geneva
Derry, J. M. J. (author)
Mecham, B. (author)
Trialomics
Spégel, P (author)
Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Diabetes - Molecular Metabolism,Lund University Research Groups,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
Mulder, H (author)
Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
Costa, I. G. (author)
RWTH Aachen University
Zhang, E (author)
Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
Rosengren, Anders H., 1978 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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 (creator_code:org_t)
2017-06-06
2017
English.
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca 2+-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Keyword

Animalia
Journal Article

Publication and Content Type

ref (subject category)
art (subject category)

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