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Volta, F. ; Scerbo, M.J. ; Seelig, A. ; Wagner, R. ; O'Brien, N. ; Gerst, F. ; Fritsche, A. ; Häring, H.-U. ; Zeigerer, A. ; Ullrich, S. ; Gerdes, J.M.

Glucose homeostasis is regulated by pancreatic beta-cell cilia via endosomal EphA-processing.

Nat. Commun. 10:5686 (2019)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
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Diabetes mellitus affects one in eleven adults worldwide. Most suffer from Type 2 Diabetes which features elevated blood glucose levels and an inability to adequately secrete or respond to insulin. Insulin producing beta-cells have primary cilia which are implicated in the regulation of glucose metabolism, insulin signaling and secretion. To better understand how beta-cell cilia affect glucose handling, we ablate cilia from mature beta-cells by deleting key cilia component Ift88. Here we report that glucose homeostasis and insulin secretion deteriorate over 12 weeks post-induction. Cilia/basal body components are required to suppress spontaneous auto-activation of EphA3 and hyper-phosphorylation of EphA receptors inhibits insulin secretion. In beta-cells, loss of cilia/basal body function leads to polarity defects and epithelial-to-mesenchymal transition. Defective insulin secretion from IFT88-depleted human islets and elevated pEPHA3 in islets from diabetic donors both point to a role for cilia/basal body proteins in human glucose homeostasis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Bardet-biedl-syndrome; Insulin-secretion; Disruption; Receptor; Gtpase; Islets; Mouse; Mass; Endocytosis; Proteins
Language
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 10, Issue: 1, Pages: , Article Number: 5686 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Regeneration Research (IDR)
Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Diabetes and Cancer (IDC)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-501900-233
G-502400-001
G-501900-254
DOI 10.1038/s41467-019-12953-5
WOS ID WOS:000502252800001
PubMed ID 31831727
Erfassungsdatum 2019-12-19
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