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Polyol pathway and diabetic nephropathy revisited: Early tubular cell changes and glomerulopathy in diabetic mice overexpressing human aldose reductase
Aims/Introduction: The polyol pathway has long been involved in the pathogenesis of diabetic nephropathy. It remains still unclear, however, how the polyol pathway is implicated in this process. We explored the effects of the enhanced polyol pathway on renocortical tubular cells and glomeruli in ex...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015536/ https://www.ncbi.nlm.nih.gov/pubmed/24843470 http://dx.doi.org/10.1111/j.2040-1124.2010.00071.x |
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author | Hashimoto, Yasuhiro Yamagishi, Shin‐Ichiro Mizukami, Hiroki Yabe‐Nishimura, Chihiro Lim, Sun Woo Kwon, H Moo Yagihashi, Soroku |
author_facet | Hashimoto, Yasuhiro Yamagishi, Shin‐Ichiro Mizukami, Hiroki Yabe‐Nishimura, Chihiro Lim, Sun Woo Kwon, H Moo Yagihashi, Soroku |
author_sort | Hashimoto, Yasuhiro |
collection | PubMed |
description | Aims/Introduction: The polyol pathway has long been involved in the pathogenesis of diabetic nephropathy. It remains still unclear, however, how the polyol pathway is implicated in this process. We explored the effects of the enhanced polyol pathway on renocortical tubular cells and glomeruli in experimentally‐induced diabetes. Materials and Methods: Transgenic mice (Tg) overexpressing human aldose reductase were made diabetic by streptozotocin and followed for 8 weeks. Renocortical pathology, expressions of tonicity‐responsive enhancer binding protein (TonEBP) and carboxymethyllysine of advanced glycation end‐products, were examined. Wild‐type non‐transgenic mice (Wt) were also made diabetic and served as controls. Results: Diabetic Tg showed augmented expression of TonEBP in renocortical tubular cells with vacuolated degenerative changes. These structural changes were associated with pronounced deposition of carboxymethyllysine. There was a significant increase in kidney weight, glomerular size, and mesangial area in diabetic animals and there was a trend for more severe changes in these measures in diabetic transgenic mice compared with those in control diabetic mice. Treatment with aldose reductase inhibitor significantly prevented polyol accumulation, mesangial expansion and expressions of TonEBP and carboxymethyllysine in diabetic Tg, but its effects on the renal structure were equivocal in control diabetic Wt. Conclusions: Our findings suggest that tubuloglomerular change might contribute to early diabetic nephropathy under the influence of the enhanced polyol pathway. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00071.x, 2010) |
format | Online Article Text |
id | pubmed-4015536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-40155362014-05-19 Polyol pathway and diabetic nephropathy revisited: Early tubular cell changes and glomerulopathy in diabetic mice overexpressing human aldose reductase Hashimoto, Yasuhiro Yamagishi, Shin‐Ichiro Mizukami, Hiroki Yabe‐Nishimura, Chihiro Lim, Sun Woo Kwon, H Moo Yagihashi, Soroku J Diabetes Investig Articles Aims/Introduction: The polyol pathway has long been involved in the pathogenesis of diabetic nephropathy. It remains still unclear, however, how the polyol pathway is implicated in this process. We explored the effects of the enhanced polyol pathway on renocortical tubular cells and glomeruli in experimentally‐induced diabetes. Materials and Methods: Transgenic mice (Tg) overexpressing human aldose reductase were made diabetic by streptozotocin and followed for 8 weeks. Renocortical pathology, expressions of tonicity‐responsive enhancer binding protein (TonEBP) and carboxymethyllysine of advanced glycation end‐products, were examined. Wild‐type non‐transgenic mice (Wt) were also made diabetic and served as controls. Results: Diabetic Tg showed augmented expression of TonEBP in renocortical tubular cells with vacuolated degenerative changes. These structural changes were associated with pronounced deposition of carboxymethyllysine. There was a significant increase in kidney weight, glomerular size, and mesangial area in diabetic animals and there was a trend for more severe changes in these measures in diabetic transgenic mice compared with those in control diabetic mice. Treatment with aldose reductase inhibitor significantly prevented polyol accumulation, mesangial expansion and expressions of TonEBP and carboxymethyllysine in diabetic Tg, but its effects on the renal structure were equivocal in control diabetic Wt. Conclusions: Our findings suggest that tubuloglomerular change might contribute to early diabetic nephropathy under the influence of the enhanced polyol pathway. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00071.x, 2010) Blackwell Publishing Ltd 2011-04-07 2010-10-21 /pmc/articles/PMC4015536/ /pubmed/24843470 http://dx.doi.org/10.1111/j.2040-1124.2010.00071.x Text en © 2010 Asian Association for the Study of Diabetes and Blackwell Publishing Asia Pty Ltd |
spellingShingle | Articles Hashimoto, Yasuhiro Yamagishi, Shin‐Ichiro Mizukami, Hiroki Yabe‐Nishimura, Chihiro Lim, Sun Woo Kwon, H Moo Yagihashi, Soroku Polyol pathway and diabetic nephropathy revisited: Early tubular cell changes and glomerulopathy in diabetic mice overexpressing human aldose reductase |
title | Polyol pathway and diabetic nephropathy revisited: Early tubular cell changes and glomerulopathy in diabetic mice overexpressing human aldose reductase |
title_full | Polyol pathway and diabetic nephropathy revisited: Early tubular cell changes and glomerulopathy in diabetic mice overexpressing human aldose reductase |
title_fullStr | Polyol pathway and diabetic nephropathy revisited: Early tubular cell changes and glomerulopathy in diabetic mice overexpressing human aldose reductase |
title_full_unstemmed | Polyol pathway and diabetic nephropathy revisited: Early tubular cell changes and glomerulopathy in diabetic mice overexpressing human aldose reductase |
title_short | Polyol pathway and diabetic nephropathy revisited: Early tubular cell changes and glomerulopathy in diabetic mice overexpressing human aldose reductase |
title_sort | polyol pathway and diabetic nephropathy revisited: early tubular cell changes and glomerulopathy in diabetic mice overexpressing human aldose reductase |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015536/ https://www.ncbi.nlm.nih.gov/pubmed/24843470 http://dx.doi.org/10.1111/j.2040-1124.2010.00071.x |
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