title: Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway.
abstract: The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiang Su key Laboratory for Efficacy and Safety Evaluation of Chinese Medicine, Nanjing 210023, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiang Su key Laboratory for Efficacy and Safety Evaluation of Chinese Medicine, Nanjing 210023, China.
authors.forename: Gao-Hong
authors.initials: GH
authors.lastname: Lv
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiang Su key Laboratory for Efficacy and Safety Evaluation of Chinese Medicine, Nanjing 210023, China.
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Dai
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Department of Chinese Medicine Resources, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiang Su key Laboratory for Efficacy and Safety Evaluation of Chinese Medicine, Nanjing 210023, China. Electronic address: hqxu309@aliyun.com.
authors.forename: Hui-Qin
authors.initials: HQ
authors.lastname: Xu
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000235:genetics / Q000378:metabolism*; D004032:Diet / Q000009:adverse effects*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D010179:Pancreas / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase
keywords: AGEs/RAGE/ROS pathway; Advanced glycation end products; Diabetic vascular complications; Reactive oxygen species; c-Reactive protein