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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes. / Axelsson, Annika; Mahdi, T; Nenonen, H A; Singh, Tania; Hänzelmann, S; Wendt, A; Bagge, Annika; Reinbothe, T M; Millstein, J; Yang, X; Zhang, B.; Gusmao, E G; Shu, L; Szabat, M; Tang, Y; Wang, Jinling; Salö, Sofia; Eliasson, L; Artner, I; Fex, M; Johnson, J D; Wollheim, C B; Derry, J M J; Mecham, B; Spégel, P; Mulder, H; Costa, Ivan G; Zhang, E; Rosengren, A H.

I: Nature Communications, Vol. 8, 06.06.2017, s. 15652.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Axelsson, A, Mahdi, T, Nenonen, HA, Singh, T, Hänzelmann, S, Wendt, A, Bagge, A, Reinbothe, TM, Millstein, J, Yang, X, Zhang, B, Gusmao, EG, Shu, L, Szabat, M, Tang, Y, Wang, J, Salö, S, Eliasson, L, Artner, I, Fex, M, Johnson, JD, Wollheim, CB, Derry, JMJ, Mecham, B, Spégel, P, Mulder, H, Costa, IG, Zhang, E & Rosengren, AH 2017, 'Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes', Nature Communications, vol. 8, s. 15652. https://doi.org/10.1038/ncomms15652

APA

Axelsson, A., Mahdi, T., Nenonen, H. A., Singh, T., Hänzelmann, S., Wendt, A., ... Rosengren, A. H. (2017). Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes. Nature Communications, 8, 15652. https://doi.org/10.1038/ncomms15652

CBE

Axelsson A, Mahdi T, Nenonen HA, Singh T, Hänzelmann S, Wendt A, Bagge A, Reinbothe TM, Millstein J, Yang X, Zhang B, Gusmao EG, Shu L, Szabat M, Tang Y, Wang J, Salö S, Eliasson L, Artner I, Fex M, Johnson JD, Wollheim CB, Derry JMJ, Mecham B, Spégel P, Mulder H, Costa IG, Zhang E, Rosengren AH. 2017. Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes. Nature Communications. 8:15652. https://doi.org/10.1038/ncomms15652

MLA

Vancouver

Author

Axelsson, Annika ; Mahdi, T ; Nenonen, H A ; Singh, Tania ; Hänzelmann, S ; Wendt, A ; Bagge, Annika ; Reinbothe, T M ; Millstein, J ; Yang, X ; Zhang, B. ; Gusmao, E G ; Shu, L ; Szabat, M ; Tang, Y ; Wang, Jinling ; Salö, Sofia ; Eliasson, L ; Artner, I ; Fex, M ; Johnson, J D ; Wollheim, C B ; Derry, J M J ; Mecham, B ; Spégel, P ; Mulder, H ; Costa, Ivan G ; Zhang, E ; Rosengren, A H. / Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes. I: Nature Communications. 2017 ; Vol. 8. s. 15652.

RIS

TY - JOUR

T1 - Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes

AU - Axelsson, Annika

AU - Mahdi, T

AU - Nenonen, H A

AU - Singh, Tania

AU - Hänzelmann, S

AU - Wendt, A

AU - Bagge, Annika

AU - Reinbothe, T M

AU - Millstein, J

AU - Yang, X

AU - Zhang, B.

AU - Gusmao, E G

AU - Shu, L

AU - Szabat, M

AU - Tang, Y

AU - Wang, Jinling

AU - Salö, Sofia

AU - Eliasson, L

AU - Artner, I

AU - Fex, M

AU - Johnson, J D

AU - Wollheim, C B

AU - Derry, J M J

AU - Mecham, B

AU - Spégel, P

AU - Mulder, H

AU - Costa, Ivan G

AU - Zhang, E

AU - Rosengren, A H

PY - 2017/6/6

Y1 - 2017/6/6

N2 - 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.

AB - 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.

KW - Journal Article

UR - http://www.scopus.com/inward/record.url?scp=85020265594&partnerID=8YFLogxK

U2 - 10.1038/ncomms15652

DO - 10.1038/ncomms15652

M3 - Article

VL - 8

SP - 15652

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -