Abstract
Background. The notion that diabetic nephropathy is the leading cause of renal fibrosis prompted us to investigate the effects of blood glucose fluctuation (BGF) under high glucose condition on kidney in the mice. Methods. The diabetic and BGF animal models were established in this study. Immunohistochemistry, Western blot, and RT-PCR analysis were applied to detect the expression of type I collagen, matrix metalloproteinase-1 (MMP1), metalloproteinase inhibitor 1 (TIMP1), transforming growth factor beta 1 (TGF-β1), phosphorylated-ERK, p38, smad2/3, and Akt. Results. BGF treatment increased type I collagen synthesis by two times compared with the control. The expression of MMP1 was reduced markedly while TIMP1 synthesis was enhanced after BGF treatment. ERK phosphorylation exhibits a significant increase in the mice treated with BGF. Furthermore, BGF can markedly upregulate TGF-β1 expression. The p-smad2 showed 2-fold increases compared with the only diabetic mice. However, p-AKT levels were unchanged after BGF treatment. Conclusions. These data demonstrate that BGF can accelerate the trend of kidney fibrosis in diabetic mice by increasing collagen production and inhibiting collagen degradation. Both ERK/MAPK and TGF-β/smad signaling pathways seem to play a role in the development of kidney fibrosis accelerated by blood glucose fluctuation.
Highlights
Diabetes can cause a wide range of health complications such as atherosclerosis, cardiac dysfunction, retinopathy, and nephropathy
The results showed that type I collagen expression in the kidney increased markedly after blood glucose fluctuation (BGF) treatment when compared with the only diabetic mice and controls (Figure 2(a))
Previous study indicates that repetitive postprandial fluctuation in glucose concentration evokes monocyte adhesion to endothelial cells, enhances endothelial cell apoptosis, and accelerates atherosclerosis that was worse than that induced by stable hyperglycemia in vivo [11,12,13]
Summary
Diabetes can cause a wide range of health complications such as atherosclerosis, cardiac dysfunction, retinopathy, and nephropathy. The side effects of hyperglycemia can be categorized into two types, persistent elevation of blood glucose (BG) levels and blood glucose fluctuation (BGF) [1], which are closely correlated with the DM prognosis, pathogenesis, and complications. The notion that diabetic nephropathy is the leading cause of renal fibrosis prompted us to investigate the effects of blood glucose fluctuation (BGF) under high glucose condition on kidney in the mice. These data demonstrate that BGF can accelerate the trend of kidney fibrosis in diabetic mice by increasing collagen production and inhibiting collagen degradation. Both ERK/MAPK and TGF-β/smad signaling pathways seem to play a role in the development of kidney fibrosis accelerated by blood glucose fluctuation
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