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Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing
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 metabol...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908661/ https://www.ncbi.nlm.nih.gov/pubmed/31831727 http://dx.doi.org/10.1038/s41467-019-12953-5 |
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author | 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. |
author_facet | 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. |
author_sort | Volta, Francesco |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6908661 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69086612019-12-16 Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing 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. Nat Commun Article 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. Nature Publishing Group UK 2019-12-12 /pmc/articles/PMC6908661/ /pubmed/31831727 http://dx.doi.org/10.1038/s41467-019-12953-5 Text en © The Author(s) 2019, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article 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. Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing |
title | Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing |
title_full | Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing |
title_fullStr | Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing |
title_full_unstemmed | Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing |
title_short | Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing |
title_sort | glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal epha-processing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908661/ https://www.ncbi.nlm.nih.gov/pubmed/31831727 http://dx.doi.org/10.1038/s41467-019-12953-5 |
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