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IGFBP-3 Inhibits Cytokine-Induced Insulin Resistance and Early Manifestations of Atherosclerosis

Title
IGFBP-3 Inhibits Cytokine-Induced Insulin Resistance and Early Manifestations of Atherosclerosis
Authors
Lathika Mohanraj;Ho-Seong Kim;Youngman Oh;Jung Hyun Kim;Woo Jung Lee;Yong-Jae Lee;Hye-Jung Shin;Ki Eun Kim;Qing Cai;Wei Li
Issue Date
2013
Journal Title
PLoS One
ISSN
1932-6203
Citation
PLoS One, Vol.8(1) : e55084, 2013
Abstract
Metabolic syndrome is associated with visceral obesity, insulin resistance and an increased risk of cardiovascular diseases. Visceral fat tissue primarily consists of adipocytes that secrete cytokines leading to a state of systemic inflammation in obese conditions. One of the IGF-independent functions of IGFBP-3 is its role as an anti-inflammatory molecule. Our study in obese adolescents show a decrease in total IGFBP-3 levels and increase in proteolyzed IGFBP-3 in circulation when compared to their normal counterparts and establishes a positive correlation between IGFBP-3 proteolysis and adiposity parameters as well as insulin resistance. In human adipocytes, we show that IGFBP-3 inhibits TNF-α-induced NF-κB activity in an IGF-independent manner, thereby restoring the deregulated insulin signaling and negating TNF-α-induced inhibition of glucose uptake. IGFBP-3 further inhibits TNF-α, CRP and high glucose-induced NF-κB activity in human aortic endothelial cells (HAECs) and subsequently suppresses monocyte adhesion to HAEC through the IGFBP-3 receptor. In conclusion, these findings suggest that reduced levels of IGFBP-3 in circulation and reduced expression of IGFBP-3 in macrophages in obesity may result in suppression of its anti-inflammatory functions and therefore IGFBP-3 may present itself as a therapeutic for obesity-induced insulin resistance and for events occurring in the early stages of atherosclerosis.
URI

http://ir.ymlib.yonsei.ac.kr/handle/22282913/86323
DOI
10.1371/journal.pone.0055084
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Pediatrics
Yonsei Authors
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