Decreased Expression of Cilia Genes in Pancreatic Islets as a Risk Factor for Type 2 Diabetes in Mice and Humans

被引：37
|
作者：
Kluth, Oliver [1 ,2 ]
Stadion, Mandy [1 ,2 ]
Gottmann, Pascal [1 ,2 ]
Aga, Heja [1 ,2 ]
Jaehnert, Markus [1 ,2 ]
Scherneck, Stephan [1 ,3 ]
Vogel, Heike [1 ,2 ]
Krus, Ulrika [4 ]
Seelig, Anett [2 ,5 ]
Ling, Charlotte [4 ]
Gerdes, Jantje [2 ,5 ]
Schuermann, Annette [1 ,2 ,6 ]
机构：
[1] German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Expt Diabetol, Nuthetal, Germany
[2] German Ctr Diabet Res DZD, Munich, Germany
[3] Tech Univ Carolo Wilhelmina Braunschweig, Inst Pharmacol Toxicol & Clin Pharm, Braunschweig, Germany
[4] Lund Univ, Dept Clin Sci, Malmo, Sweden
[5] Helmholtz Ctr Munich, Inst Diabet & Regenerat Res, Munich, Germany
[6] Univ Potsdam, Inst Nutr Sci, Nuthetal, Germany
来源：
CELL REPORTS | 2019年 / 26卷 / 11期
基金：
瑞典研究理事会;
关键词：
BARDET-BIEDL SYNDROME; OBESITY; MECHANISMS; DIFFERENTIATION; CILIOPATHIES; DISRUPTION;
D O I：
10.1016/j.celrep.2019.02.056
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
An insufficient adaptive beta-cell compensation is a hallmark of type 2 diabetes (T2D). Primary cilia function as versatile sensory antennae regulating various cellular processes, but their role on compensatory beta-cell replication has not been examined. Here, we identify a significant enrichment of downregulated, cilia-annotated genes in pancreatic islets of diabetes-prone NZO mice as compared with diabetes-resistant B6-ob/ob mice. Among 327 differentially expressed mouse cilia genes, 81 human orthologs are also affected in islets of diabetic donors. Islets of nondiabetic mice and humans show a substantial overlap of upregulated cilia genes that are linked to cell-cycle progression. The shRNA-mediated suppression of KIF3A, essential for ciliogenesis, impairs division of MINE beta cells as well as in dispersed primary mouse and human islet cells, as shown by decreased BrdU incorporation. These findings demonstrate the substantial role of cilia-gene regulation on islet function and T2D risk.
引用
收藏
页码：3027 / +
页数：13
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