Mechanistic study of endogenous skin lesions in diabetic rats

• Published in: Experimental dermatology Vol. 19; no. 12; pp. 1088 - 1095
• Main Authors: Chen, Xiang-fang, Lin, Wei-dong, Lu, Shu-liang, Xie, Ting, Ge, Kui, Shi, Yong-quan, Zou, Jun-jie, Liu, Zhi-min, Liao, Wan-qing
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2010; Blackwell
• Subjects: advanced glycation end products; Animals; Apoptosis - drug effects; Biological and medical sciences; Cell Cycle - drug effects; Cell Line; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Dermatology; Diabetes Complications - blood; Diabetes Complications - etiology; Diabetes Complications - metabolism; Diabetes Complications - pathology; diabetes mellitus; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelial Cells - drug effects; Endothelial Cells - pathology; Epidermis - pathology; Epithelial Cells - drug effects; Epithelial Cells - pathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucose - metabolism; Glutathione - blood; Glycation End Products, Advanced - blood; Glycation End Products, Advanced - metabolism; Glycation End Products, Advanced - pharmacology; Male; Malondialdehyde - blood; Medical sciences; Microvessels - pathology; Oxidative Stress; Rats; Rats, Sprague-Dawley; Serum Albumin - pharmacology; Serum Albumin, Human; skin; Skin - metabolism; Skin - pathology; Skin Diseases - blood; Skin Diseases - etiology; Skin Diseases - metabolism; Skin Diseases - pathology; Endocrinopathy; Vertebrata; Skin disease; Mammalia; Rat; Dermatology; Animal; Diabetes mellitus; Rodentia; Skin; advanced glycation end products
• ISSN: 0906-6705; 1600-0625; 1600-0625
• DOI: 10.1111/j.1600-0625.2010.01137.x

Please cite this paper as: Mechanistic study of endogenous skin lesions in diabetic rats. Experimental Dermatology 2010; 19: 1088–1095. :  Pathological and physiological changes in dermal tissue in a rat model of diabetes mellitus (DM) were investigated. Sixteen male 8‐week‐old Sprague–Dawley rats were randomized into two groups of eight, the DM group (Group DM) and the normal control group (Group (NC) normal control). Group DM rats were injected with streptozotocin (STZ) intraperitoneally at a dose of 65 mg/kg body weight. Group NC rats were injected with the same volume of citric acid buffer. All rats were sacrificed 12 weeks later. The impact of exposure to (AGE) advanced glycation end products‐modified human serum albumin (AGE‐HSA) on epidermal cells and ECV304 cells was evaluated in cell culture experiments. The diabetic rats exhibited changes in skin tissue, including a decrease in thickness, disappearance of the multilayer epithelium structure, degeneration of collagen fibres and an increase in the infiltration of inflammatory cells, in addition to a significant increase in skin glucose and AGEs. Moreover, diabetic rats had increased plasma glycosylated protein (GSP) and malondialdehyde (MDA) and decreased plasma glutathione (GSH). The percentage of epidermal cells in S phase was similar between the two group rats; however, there was a marked decrease in the G2/M phase in Group DM. Additionally, exposure of ECV304 cells to AGE‐HSA led to a time‐dependent and dose‐dependent increase in apoptosis. Therefore, the high glucose in the skin tissue, coupled with the accumulation of toxic substances such as AGEs, promote the dysfunction of dermal cells and/or the matrix. This may be a significant mechanism of diabetes‐induced early‐stage endogenous skin damage.