The fractalkine/CX3CR1 system regulates β cell function and insulin secretion

Cell. 2013 Apr 11;153(2):413-25. doi: 10.1016/j.cell.2013.03.001.


Here, we demonstrate that the fractalkine (FKN)/CX3CR1 system represents a regulatory mechanism for pancreatic islet β cell function and insulin secretion. CX3CR1 knockout (KO) mice exhibited a marked defect in glucose and GLP1-stimulated insulin secretion, and this defect was also observed in vitro in isolated islets from CX3CR1 KO mice. In vivo administration of FKN improved glucose tolerance with an increase in insulin secretion. In vitro treatment of islets with FKN increased intracellular Ca(2+) and potentiated insulin secretion in both mouse and human islets. The KO islets exhibited reduced expression of a set of genes necessary for the fully functional, differentiated β cell state, whereas treatment of wild-type (WT) islets with FKN led to increased expression of these genes. Lastly, expression of FKN in islets was decreased by aging and high-fat diet/obesity, suggesting that decreased FKN/CX3CR1 signaling could be a mechanism underlying β cell dysfunction in type 2 diabetes.

Publication types

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

MeSH terms

  • Adult
  • Aging
  • Animals
  • CX3C Chemokine Receptor 1
  • Cadaver
  • Chemokine CX3CL1 / administration & dosage
  • Chemokine CX3CL1 / metabolism
  • Diet, High-Fat
  • Gene Expression
  • Glucose / metabolism
  • Humans
  • Hyperglycemia / metabolism
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism*
  • Signal Transduction*


  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human
  • Chemokine CX3CL1
  • Cx3cr1 protein, mouse
  • Insulin
  • Receptors, Chemokine
  • Glucose