Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway

Chin J Nat Med. 2016 Nov;14(11):844-855. doi: 10.1016/S1875-5364(16)30101-7.

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.

Keywords: AGEs/RAGE/ROS pathway; Advanced glycation end products; Diabetic vascular complications; Reactive oxygen species; c-Reactive protein.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Angiopathies / genetics
  • Diabetic Angiopathies / 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
  • Receptor for Advanced Glycation End Products / metabolism*
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Glycation End Products, Advanced
  • Interleukin-6
  • Reactive Oxygen Species
  • Receptor for Advanced Glycation End Products
  • Tumor Necrosis Factor-alpha
  • Superoxide Dismutase