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.
Subject(s)
Animals , Humans , Male , Mice , Diabetes Mellitus, Experimental , Metabolism , Diabetic Angiopathies , Genetics , Metabolism , Diet , Glycation End Products, Advanced , Metabolism , Interleukin-6 , Metabolism , Kidney , Metabolism , 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 , MetabolismABSTRACT
Objective: To investigate the protective effect and the mechanism of loganin (an active component in Cornus officinalis) on the endoplasmic reticulum (ER) stress of glomerular mesangial cells (GMCs) induced by advanced glycation end products (AGEs). Methods: Human GMCs were cultured in vitro and divided into control group, model group (AGEs group), loganin group, and amino guanidine group (set as positive control, 0.1, 1.0, and 10.0 μmol/L). After being incubated with loganin (final concentration of 0.1, 1.0, and 10.0 μmol/L) for 1 h, GMCs were stimulated by AGEs (200 mg/L) for 24 h. Then, the cell proliferation was measured of using MTS method. PGE2 was investigated by Elisa. Receptors of advanced glycation end products (RAGE), and ER stress-related protein like GRP78, IRE1, XBP1, and inflammatory factor NF-κB and COX-2 in GMCs were detected by Western blotting. Results: Loganin could suppress the proliferation of GMCs induced by AGEs, improve the subcellular injury of GMCs, down-regulate the expression of ER stress-related protein GRP78, IRE1, XBP1, and RAGE, reduce the inflammation-related protein NF-κB, COX-2, and the level of PGE2. Conclusion: Loganin could improve the ER stress of GMCs induced by AGEs, lessen the inflammation and subcellular injury of GMCs, its mechanism might be related to the decreased expression of RAGE and the inhibition of the IRE1 pathway.