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Fractalkine signaling in regulation of insulin secretion: Mechanisms and potential therapeutic implications?

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 l...

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Autores principales: Gregg, Brigid, Lumeng, Carey N, Bernal-Mizrachi, Ernesto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593565/
https://www.ncbi.nlm.nih.gov/pubmed/25483879
http://dx.doi.org/10.4161/isl.27861
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author Gregg, Brigid
Lumeng, Carey N
Bernal-Mizrachi, Ernesto
author_facet Gregg, Brigid
Lumeng, Carey N
Bernal-Mizrachi, Ernesto
author_sort Gregg, Brigid
collection PubMed
description 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.
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spelling pubmed-45935652015-10-08 Fractalkine signaling in regulation of insulin secretion: Mechanisms and potential therapeutic implications? Gregg, Brigid Lumeng, Carey N Bernal-Mizrachi, Ernesto Islets Commentary 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. Landes Bioscience 2014-02-26 /pmc/articles/PMC4593565/ /pubmed/25483879 http://dx.doi.org/10.4161/isl.27861 Text en Copyright © 2014 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Commentary
Gregg, Brigid
Lumeng, Carey N
Bernal-Mizrachi, Ernesto
Fractalkine signaling in regulation of insulin secretion: Mechanisms and potential therapeutic implications?
title Fractalkine signaling in regulation of insulin secretion: Mechanisms and potential therapeutic implications?
title_full Fractalkine signaling in regulation of insulin secretion: Mechanisms and potential therapeutic implications?
title_fullStr Fractalkine signaling in regulation of insulin secretion: Mechanisms and potential therapeutic implications?
title_full_unstemmed Fractalkine signaling in regulation of insulin secretion: Mechanisms and potential therapeutic implications?
title_short Fractalkine signaling in regulation of insulin secretion: Mechanisms and potential therapeutic implications?
title_sort fractalkine signaling in regulation of insulin secretion: mechanisms and potential therapeutic implications?
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593565/
https://www.ncbi.nlm.nih.gov/pubmed/25483879
http://dx.doi.org/10.4161/isl.27861
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