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

Publication date: 12 March 2019Source: Cell Reports, Volume 26, Issue 11Author(s): Oliver Kluth, Mandy Stadion, Pascal Gottmann, Heja Aga, Markus Jähnert, Stephan Scherneck, Heike Vogel, Ulrika Krus, Anett Seelig, Charlotte Ling, Jantje Gerdes, Annette SchürmannSummaryAn 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 MIN6 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.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research