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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.
AuthorsXing Lv, Gao-Hong Lv, Guo-Ying Dai, Hong-Mei Sun, Hui-Qin Xu
JournalChinese journal of natural medicines (Chin J Nat Med) Vol. 14 Issue 11 Pg. 844-855 (Nov 2016) ISSN: 1875-5364 [Electronic] China
PMID27914528 (Publication Type: Journal Article)
CopyrightCopyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Glycation End Products, Advanced
  • Interleukin-6
  • Reactive Oxygen Species
  • Receptor for Advanced Glycation End Products
  • Tumor Necrosis Factor-alpha
  • Superoxide Dismutase
Topics
  • Animals
  • Diabetes Mellitus, Experimental (complications, metabolism)
  • Diabetic Angiopathies (genetics, metabolism)
  • Diet (adverse effects)
  • Glycation End Products, Advanced (metabolism)
  • Humans
  • Interleukin-6 (metabolism)
  • Kidney (metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress
  • Pancreas (metabolism)
  • Reactive Oxygen Species (metabolism)
  • Receptor for Advanced Glycation End Products (genetics, metabolism)
  • Superoxide Dismutase (metabolism)
  • Tumor Necrosis Factor-alpha (metabolism)

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