Primary cilia control glucose homeostasis via islet paracrine interactions

Proc Natl Acad Sci U S A. 2020 Apr 21;117(16):8912-8923. doi: 10.1073/pnas.2001936117. Epub 2020 Apr 6.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Communication / physiology
  • Cilia / genetics
  • Cilia / metabolism*
  • Cilia / pathology
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / pathology*
  • Disease Models, Animal
  • Energy Metabolism / physiology
  • Female
  • Glucagon-Secreting Cells / metabolism
  • Glucose / metabolism*
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Signal Transduction / physiology


  • Insulin
  • Glucose
  • Calcium