If the cilia on beta cells of the pancreas do not function properly, glucose intolerance and type 2 diabetes develop. In Nature Communications, a research team from Helmholtz Zentrum München and the German Center for Diabetes Research (DZD) describes the underlying mechanism.
The insulin producing beta cells have primary cilia which are implicated in the regulation of glucose metabolism, insulin signaling and secretion. In order to understand better how these cilia influence the handling of glucose, the researchers removed the cilia from mature beta cells. They found that glucose tolerance and insulin release deteriorated significantly over twelve weeks.
These phenomena were conveyed by special binding sites on beta cells, the ephrin receptors. In this process, EphA/ephrin signals are upregulated, which suppress insulin secretion. Researchers observed similar reactions with islet cells from organ donors. The research group also evaluated data from a small cohort of 19 patients and found a correlation between ciliopathy* genes and blood sugar levels.
"We were able to show in a mouse model that cilia in the pancreas regulate direct pathways of cell-cell communication and thus control blood glucose levels," said Dr. Jantje M. Gerdes. The results of the investigations could provide a basis for future therapies - both for ciliopathies and diabetes.
* Ciliopathies are genetic disorders of the ciliated cell.
F. Volta et al., 2019: Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing. Nature Communications, doi: 10.1038/s41467-019-12953-5