Adiponectin protects endothelial cells from the damages induced by the intermittent high level of glucose
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ORIGINAL ARTICLE
Adiponectin protects endothelial cells from the damages induced by the intermittent high level of glucose Xinhua Xiao • Yuanyuan Dong • Jing Zhong Renxian Cao • Xiang Zhao • Gebo Wen • Jianghua Liu
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Received: 20 April 2011 / Accepted: 30 August 2011 / Published online: 24 September 2011 Ó Springer Science+Business Media, LLC 2011
Abstract Globular adiponectin (gAd) has anti-atherogenic effects on the vascular wall. Intermittent hyperglycemia induces endothelial cells (ECs) injury but the physiological factors that may protect against ECs damage are largely unknown. In the present study, we investigated the effect of gAd on ECs dysfunction induced by intermittent high glucose. The gAd significantly attenuated intermittent high glucose-induced apoptosis and oxidative stress in human umbilical vein endothelial cells. This was achieved by decreasing caspase-3 and 3-nitrotyrosine protein expression, increasing nitric oxide (NO) secretion and phosphorylation of Akt, AMPK, and endothelial nitric oxide synthase protein expression. Pretreatment with a phosphatidylinositol 3’ kinase (PI3K) inhibitor, LY294002, partly reversed adiponectin’s anti-apoptotic effect. Taken together, our results indicate that gAd acts as a critical physiological factor which protects against fluctuating high glucose-induced endothelial damage. It may act via attenuating apoptosis and increasing synthesis of NO through both the PI3K/AKT and AMPK signaling pathway to reduce oxidative stress and cell apoptosis. Keywords Globular adiponectin Endothelial cell Intermittent high glucose Apoptosis Oxidative stress
X. Xiao Y. Dong J. Zhong R. Cao X. Zhao G. Wen J. Liu (&) Department of Metabolism & Endocrinology, The First Affiliated Hospital, University of South China, 69 Chuanshan Road, Hengyang 421001, People’s Republic of China e-mail: [email protected]
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Introduction Endothelial cells (ECs) play a critical role in the maintenance of vascular homeostasis. Hyperglycemia has been reported to trigger and accelerate apoptosis in ECs [1]. Apoptosis in ECs is a vital event in diabetes-associated vascular diseases, and is particularly prominent in endothelial injuries caused by fluctuating hyperglycemia [2–4]. Although the protective effect of adiponectin in ECs against constant hyperglycemia is well known, the effect of adiponectin in ECs against the fluctuating glucose levels remains to be fully established. Adipose tissue secretes a variety of adipokines to modulate endothelial function [5]. Among them, adiponectin is known to be anti-atherogenic [6]. Adiponectin is present in human plasma in two different forms: full length and globular form. Both the full-length and the C-terminal globular forms have been shown to be anti-atherogenic through protecting the cellular components of blood vessels [7]. Decreased plasma level of adiponectin is associated with endothelial dysfunction seen in type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome [8]. Circulating adiponectin level is negatively correla
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