| First Author | Hughes JW | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 16 | Pages | 8912-8923 |
| PubMed ID | 32253320 | Mgi Jnum | J:290162 |
| Mgi Id | MGI:6407162 | Doi | 10.1073/pnas.2001936117 |
| Citation | Hughes JW, et al. (2020) Primary cilia control glucose homeostasis via islet paracrine interactions. Proc Natl Acad Sci U S A 117(16):8912-8923 |
| abstractText | Pancreatic islets regulate glucose homeostasis through coordinated actions of hormone-secreting cells. What underlies the function of the islet as a unit is the close approximation and communication among heterogeneous cell populations, but the structural mediators of islet cellular cross talk remain incompletely characterized. We generated mice specifically lacking beta-cell primary cilia, a cellular organelle that has been implicated in regulating insulin secretion, and found that the beta-cell cilia are required for glucose sensing, calcium influx, insulin secretion, and cross regulation of alpha- and delta-cells. Protein expression profiling in islets confirms perturbation in these cellular processes and reveals additional targets of cilia-dependent signaling. At the organism level, the deletion of beta-cell cilia disrupts circulating hormone levels, impairs glucose homeostasis and fuel usage, and leads to the development of diabetes. Together, these findings demonstrate that primary cilia not only orchestrate beta-cell-intrinsic activity but also mediate cross talk both within the islet and from islets to other metabolic tissues, thus providing a unique role of cilia in nutrient metabolism and insight into the pathophysiology of diabetes. |
