Oliver Kluth, Mandy Stadion, Pascal Gottmann, Heja Aga-Barfknecht, Markus Jähnert, Stephan Scherneck, Heike Vogel, Ulrika Krus, Anett Seelig, Charlotte Ling, Jantje Gerdes, Annette Schürmann
- 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.
MetadatenAuthor details: | Oliver Kluth, Mandy StadionORCiDGND, Pascal GottmannORCiDGND, Heja Aga-BarfknechtORCiDGND, Markus JähnertORCiD, Stephan ScherneckORCiD, Heike VogelORCiDGND, Ulrika Krus, Anett Seelig, Charlotte Ling, Jantje GerdesORCiD, Annette SchürmannORCiDGND |
---|
DOI: | https://doi.org/10.1016/j.celrep.2019.02.056 |
---|
ISSN: | 2211-1247 |
---|
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/30865891 |
---|
Title of parent work (English): | Cell reports |
---|
Publisher: | Cell Press |
---|
Place of publishing: | Maryland Heights |
---|
Publication type: | Article |
---|
Language: | English |
---|
Date of first publication: | 2019/03/12 |
---|
Publication year: | 2019 |
---|
Release date: | 2021/03/17 |
---|
Volume: | 26 |
---|
Issue: | 11 |
---|
Number of pages: | 13 |
---|
First page: | 3027 |
---|
Last Page: | 3036 |
---|
Funding institution: | German Ministry of Education and Research (BMBF: DZD)Federal Ministry of Education & Research (BMBF) [82DZD00302]; German Diabetes Association (DDG) [2017/02/21]; German Research Foundation (DFG)German Research Foundation (DFG) [SFB-958]; Swedish Research CouncilSwedish Research Council; Novo Nordisk FoundationNovo Nordisk Foundation; Linne grant [B31 5631/2006]; JDRFJuvenile Diabetes Research Foundation [1-2008-416]; EXODIAB Human Tissue Lab, Lund University; State of Brandenburg |
---|
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
---|
DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
---|
Peer review: | Referiert |
---|
Publishing method: | Open Access / Gold Open-Access |
---|
| DOAJ gelistet |
---|
License (German): | CC-BY-NC-ND - Namensnennung, nicht kommerziell, keine Bearbeitungen 4.0 International |
---|