| Autor: |
Volta, Francesco, Scerbo, M. Julia, Seelig, Anett, Wagner, Robert, O'Brien, Nils, Gerst, Felicia, Fritsche, Andreas, Häring, Hans-Ulrich, Zeigerer, Anja, Ullrich, Susanne, Gerdes, Jantje M. |
| Předmět: |
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| Zdroj: |
Nature Communications; 12/12/2019, Vol. 10 Issue 1, p1-17, 17p |
| Abstrakt: |
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 β-cells have primary cilia which are implicated in the regulation of glucose metabolism, insulin signaling and secretion. To better understand how β-cell cilia affect glucose handling, we ablate cilia from mature β-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 β-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. Primary cilia have been proposed to regulate glucose metabolism and insulin secretion in beta cells, but it is not known how. Here the authors show that primary cilia play a role in adult β-cell function via a mechanism involving endosomal EphA-processing. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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