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

Annika Axelsson, T Mahdi, H A Nenonen, Tania Singh, S Hänzelmann, A Wendt, Annika Bagge, T M Reinbothe, J Millstein, X Yang, B. Zhang, E G Gusmao, L Shu, M Szabat, Y Tang, Jinling Wang, Sofia Salö, L Eliasson, I Artner, M FexJ D Johnson, C B Wollheim, J M J Derry, B Mecham, P Spégel, H Mulder, Ivan G Costa, E Zhang, A H Rosengren

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

22 Citeringar (SciVal)


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.

Sidor (från-till)15652
TidskriftNature Communications
StatusPublished - 2017 juni 6

Ämnesklassifikation (UKÄ)

  • Endokrinologi och diabetes


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