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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...

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Autores principales: Hashimoto, Yasuhiro, Yamagishi, Shin‐Ichiro, Mizukami, Hiroki, Yabe‐Nishimura, Chihiro, Lim, Sun Woo, Kwon, H Moo, Yagihashi, Soroku
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2011
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)
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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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