作者
AS Axelsson, T Mahdi, HA Nenonen, Tania Singh, S Hänzelmann, A Wendt, Annika Bagge, TM Reinbothe, J Millstein, X Yang, B Zhang, EG Gusmao, L Shu, M Szabat, Y Tang, Jinling Wang, Sofia Salö, L Eliasson, I Artner, M Fex, JD Johnson, CB Wollheim, JMJ Derry, B Mecham, P Spégel, H Mulder, Ivan G Costa, E Zhang, AH Rosengren
发表日期
2017/6/6
期刊
Nature communications
卷号
8
期号
1
页码范围
15652
出版商
Nature Publishing Group UK
简介
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 Ca2+-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 …
学术搜索中的文章
AS Axelsson, T Mahdi, HA Nenonen, T Singh… - Nature communications, 2017