title: Fractalkine signaling in regulation of insulin secretion.
abstract: Fractalkine is a chemokine, which has been shown to play important roles in metabolic disease in both animal models and humans. Fractalkine is a key player in the accumulation of atherosclerotic plaques, and fractalkine receptor (CX3CR1) mutations have been implicated in obesity. Serum fractalkine levels have been found to be elevated in type 2 diabetic patients, but the role of fractalkine signaling on the pancreatic β cell was unclear. Recently published findings in April 2013 issue of the journal Cell by Lee and Olefsky et al. have implicated fractalkine in β-cell insulin secretion. They demonstrate that Cx3cr1 knockout mice have impaired glucose tolerance resulting from decreased insulin secretion. In addition, fractalkine administration improved glucose tolerance and induced insulin secretion. This modulation of insulin secretion was proposed to result from an increase in intracellular calcium and potentiation of insulin secretion, which occurs in a Gαi and MEK-dependent manner. They also found that Cx3cr1 knockout animals had transcriptional repression of genes important for β-cell function, specifically NeuroD, via induction of ICER-1. One important issue that remains unresolved is how CX3CR1 signaling regulates the potentiation of calcium influx and the distal events in insulin exocytosis. Finally, testing the effects of fractalkine treatment on proliferation and survival in vivo during regenerative conditions would be critical to determine the potential use of this chemokine in diabetes. While these exciting results open the possibility for new therapeutics, there are some concerns about a potential risk for exacerbation of atherosclerosis.
authors.affiliation: a Department of Pediatrics and Communicable Diseases; Division of Endocrinology, Diabetes, and Metabolism; University of Michigan; Ann Arbor, MI USA.
authors.forename: Brigid
authors.initials: B
authors.lastname: Gregg
authors.forename: Carey N
authors.initials: CN
authors.lastname: Lumeng
authors.forename: Ernesto
authors.initials: E
authors.lastname: Bernal-Mizrachi
mesh_terms: D000818:Animals; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D019707:Receptors, Chemokine / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007328:Insulin; D019707:Receptors, Chemokine
keywords: CX3CL1; CX3CR1; diabetes; fractalkine; insulin; insulin secretion; islets; β-cell