A Novel Pathway for Regulation of Insulin Secretion by Fractalkine and CX3CR1 System (LB772)

Fractalkine (FKN) (CX3CL1) and its receptor CX3CR1 mediate cell-to-cell interactions in different tissues. Here, we demonstrate that the FKN/CX3CR1 system represents a novel regulatory mechanism for pancreatic islet beta cell function and insulin secretion. CX3CR1 KO mice exhibit glucose intolerance with normal insulin sensitivity, due to a marked beta cell defect in glucose and GLP1-stimulated insulin secretion. The defect in insulin secretion 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 Ca2+ level and potentiated insulin secretion. The KO islets exhibited reduced expression of a set of genes which are necessary for the fully functional, differentiated beta cell state, whereas, treatment of WT islets with FKN leads to increased expression of these genes. Lastly, expression of FKN in islets was decreased by aging and HFD/obesity...