详细记录  
题名:Fractalkine signaling in regulation of insulin secretion: Mechanisms and potential therapeutic implications?
作者:GREGG B; LUMENG CN; BERNAL-MIZRACHI E;
来源:Islets. 2014 Feb 26;6(1). [ IF= 1.54 ] ]
URL :N U L L
日期:20140317
摘要: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 beta cell was unclear. Recently published findings in
April 2013 issue of the journal Cell by Lee and Olefsky et al. have implicated
fractalkine in beta-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 Galphai and MEK-dependent manner. They also found that Cx3cr1
knockout animals had transcriptional repression of genes important for beta-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.

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