| First Author | Volta F | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 5686 |
| PubMed ID | 31831727 | Mgi Jnum | J:286720 |
| Mgi Id | MGI:6388323 | Doi | 10.1038/s41467-019-12953-5 |
| Citation | Volta F, et al. (2019) Glucose homeostasis is regulated by pancreatic beta-cell cilia via endosomal EphA-processing. Nat Commun 10(1):5686 |
| abstractText | 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. |
