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

Research output: Contribution to journalArticle


title = "Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes",
abstract = "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.",
keywords = "Journal Article",
author = "Annika Axelsson and T Mahdi and Nenonen, {H A} and Tania Singh and S H{\"a}nzelmann and A Wendt and Annika Bagge and Reinbothe, {T M} and J Millstein and X Yang and B. Zhang and Gusmao, {E G} and L Shu and M Szabat and Y Tang and Jinling Wang and Sofia Sal{\"o} and L Eliasson and I Artner and M Fex and Johnson, {J D} and Wollheim, {C B} and Derry, {J M J} and B Mecham and P Sp{\'e}gel and H Mulder and Costa, {Ivan G} and E Zhang and Rosengren, {A H}",
year = "2017",
month = jun,
day = "6",
doi = "10.1038/ncomms15652",
language = "English",
volume = "8",
pages = "15652",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",