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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)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Bardet-biedl-syndrome; Insulin-secretion; Disruption; Receptor; Gtpase; Islets; Mouse; Mass; Endocytosis; Proteins
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 10, Heft: 1, Seiten: , Artikelnummer: 5686 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Regeneration Research (IDR)
Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Diabetes and Cancer (IDC)