Insulin Prevents Latent Skin Lesions by Inhibiting the Generation of Advanced Glycation End Products in Streptozotocin-I

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Insulin Prevents Latent Skin Lesions by Inhibiting the Generation of Advanced Glycation End Products in Streptozotocin-Induced Diabetic Rats Xiangfang Chen & Weidong Lin & Shuliang Lu & Yongquan Shi & Junjie Zou & Zhimin Liu & Wanqing Liao

Published online: 2 June 2009 # Humana Press Inc. 2009

Abstract The preventive effect of insulin on latent skin lesions in streptozotocin-induced diabetic rats was investigated. Diabetes was induced in 72 male Sprague–Dawley rats, with 36 rats serving as the control group. Half of the diabetic rats were treated with insulin, and the other half were injected with vehicle. Skin tissues were collected 4, 8, and 12 weeks after the initiation of insulin therapy for measurement of glucose, collagen-related fluorescence and advanced glycation end product (AGE) expression, and histological observation. The diabetic rats exhibited changes in skin tissue, including a decrease in thickness, disappearance of the multilayer epithelium structure, degeneration of collagen fibers, and an increase in the infiltration of inflammatory cells, in addition to a significant increase in blood glucose and AGE expression. These effects were greatly

Xiangfang Chen and Weidong Lin contributed equally to this work.

: J. :Zou : Z. :Liu X. Chen XF. Chen: :Y.YQ. ShiShi JJ. Zou ZM. (*) Liu (*) Department of Endocrinology, Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China e-mail: [email protected] WD. Lin W. Lin Department of Burns, Shanghai Fire Corps Hospital Chinese People’s Armed Police, Shanghai 200443, China S. LuLu SL. Shanghai Burns Institute, Burns Department of Ruijin Hospital, Jiaotong University, Shanghai 20025, China W. Liao (*) WQ. Liao (*) Department of Dermatology, Chang Zheng Hospital, Second Military Medical University, Shanghai 200003, China e-mail: [email protected]

ameliorated by insulin therapy. Insulin therapy in early-stage diabetes mellitus prevents potential skin lesions, possibly by inhibiting AGE formation and inflammatory reactions following glycemic control. Keywords diabetes mellitus . advanced glycation end products . insulin

Introduction Skin complications of diabetic mellitus (DM) are a serious problem [1], and the incidence of lower-extremity amputations related to diabetes is increasing worldwide. In the USA, such amputations are estimated to cost almost $2 billion and account for 2,600 patient-years in hospital annually [2]. Up to 80% of these amputations are preceded by foot ulceration [3]. Thus, better understanding of the etiopathogenesis of diabetic skin disorders is critical for identifying effective therapeutic measures. Currently, microvascular dysfunction and nerve impairment are considered to be major contributors to the initiation of diabetic skin disorders [4]. Moreover, recent studies have confirmed that most microvascular abnormalities occur in early-stage DM, when impaired glucose tolerance is prevalent [5]. Good glycemic control in early DM is beneficial for reversing microvascular dysfunction [6], suggesting that hyper

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