Primary cilia control glucose homeostasis via islet paracrine interactions

Jing W. Hughes, Jung Hoon Cho, Hannah E. Conway, Michael R. DiGruccio, Xue Wen Ng, Henry F. Roseman, Damien Abreu, Fumihiko Urano, David W. Piston

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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 β-cell primary cilia, a cellular organelle that has been implicated in regulating insulin secretion, and found that the β-cell cilia are required for glucose sensing, calcium influx, insulin secretion, and cross regulation of α- and δ-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 β-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 β-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.

Original languageEnglish
Pages (from-to)8912-8923
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number16
DOIs
StatePublished - Apr 21 2020

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