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AhR deficiency improves insulin sensitivity.

Many man-made pollutants activate the aryl hydrocarbon receptor (AhR) and are risk factors for type 2 diabetes. In addition, AhR signaling affects molecular clock genes to influence glucose metabolism. Wang et al. (p. 1739) investigated mechanisms by which AhR activation affects glucose metabolism by examining glucose tolerance, insulin resistance, expression of peroxisome proliferator-activated receptor-[alpha] (PPAR-[alpha]) and genes affecting glucose metabolism or fatty acid oxidation, and clock gene rhythms in wild type (WT) and AhR-deficient [knockout (KO)] mice. The authors used AhR agonists and small interfering RNA (siRNA) to examine the effect of AhR on PPAR-[alpha] expression and glycolysis in the Hepa-lclc7 (c7) liver cell line, and Bmall (brain, muscle ARNT-like protein 1) siRNA and Ahr or Bmall expression plasmids to analyze the effect of BMAL1 on PPAR-[alpha] expression in c7 cells. The authors found enhanced insulin sensitivity and improved glucose tolerance in KO mice, as well as altered rhythms of BMALl and blood glucose. In c7 cells, AhR agonists induced PPAR-[alpha] expression, and Ahr and Bmall siRNA both reduced PPAR-[alpha] and metabolism genes. The authors conclude that their results indicate a fink between AhR signaling, circadian rhythms, and glucose metabolism.

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Title Annotation:Research
Publication:Environmental Health Perspectives
Article Type:Brief article
Geographic Code:1USA
Date:Dec 1, 2011
Words:196
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