| Literature DB >> 30865891 |
Oliver Kluth1, Mandy Stadion1, Pascal Gottmann1, Heja Aga1, Markus Jähnert1, Stephan Scherneck2, Heike Vogel1, Ulrika Krus3, Anett Seelig4, Charlotte Ling3, Jantje Gerdes4, Annette Schürmann5.
Abstract
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 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.Entities:
Keywords: New Zealand Obese mouse; beta-cell proliferation; cilia genes; human pancreatic islets; islet transcriptomics; pathway enrichment analysis; primary cilia; type 2 diabetes
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Year: 2019 PMID： 30865891 DOI： 10.1016/j.celrep.2019.02.056
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423