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Hyperglycemia induces spermatogenic disruption via major pathways of diabetes pathogenesis
Diabetes-induced hyperglycemia has previously been shown to impact on male sub-/infertility, however, still little is known about the underlying mechanisms. In the present study we have addressed three major biochemical pathways implicated in the pathogenesis of hyperglycemia induced organ damage (t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736974/ https://www.ncbi.nlm.nih.gov/pubmed/31506549 http://dx.doi.org/10.1038/s41598-019-49600-4 |
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author | Maresch, Constanze C. Stute, Dina C. Fleming, Thomas Lin, Jihong Hammes, Hans-Peter Linn, Thomas |
author_facet | Maresch, Constanze C. Stute, Dina C. Fleming, Thomas Lin, Jihong Hammes, Hans-Peter Linn, Thomas |
author_sort | Maresch, Constanze C. |
collection | PubMed |
description | Diabetes-induced hyperglycemia has previously been shown to impact on male sub-/infertility, however, still little is known about the underlying mechanisms. In the present study we have addressed three major biochemical pathways implicated in the pathogenesis of hyperglycemia induced organ damage (the advanced glycation end product (AGE) formation pathway, the diacylglycerol-protein kinase C pathway (PKC), and the polyol pathway) in both testis and epididymis of the Ins2(Akita) mouse model of Type 1 diabetes (T1DM). Hyperglycemia activated both the PKC and the polyol pathway in a significant and progressive manner within the testis, but not within the epididymis. While the AGE receptor was ubiquitiously expressed in the testis, concentrations of precursor methylglyoxal and AGE carboxymethyllysine were increased in both epididymis and testis in diabetic mice. However, AGEs did not activate intracellular pathways of ERK1, ERK2, Rela, Nrf-2, IkBkB, NFkB except CDC42, Akt1. In conclusion, two of the major pathways of hyperglycemia-induced organ damage were clearly activated within the testis of T1DM mice. This provides therapeutical opportunities in the treatment of diabetic male reproductive dysfunction. |
format | Online Article Text |
id | pubmed-6736974 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67369742019-09-20 Hyperglycemia induces spermatogenic disruption via major pathways of diabetes pathogenesis Maresch, Constanze C. Stute, Dina C. Fleming, Thomas Lin, Jihong Hammes, Hans-Peter Linn, Thomas Sci Rep Article Diabetes-induced hyperglycemia has previously been shown to impact on male sub-/infertility, however, still little is known about the underlying mechanisms. In the present study we have addressed three major biochemical pathways implicated in the pathogenesis of hyperglycemia induced organ damage (the advanced glycation end product (AGE) formation pathway, the diacylglycerol-protein kinase C pathway (PKC), and the polyol pathway) in both testis and epididymis of the Ins2(Akita) mouse model of Type 1 diabetes (T1DM). Hyperglycemia activated both the PKC and the polyol pathway in a significant and progressive manner within the testis, but not within the epididymis. While the AGE receptor was ubiquitiously expressed in the testis, concentrations of precursor methylglyoxal and AGE carboxymethyllysine were increased in both epididymis and testis in diabetic mice. However, AGEs did not activate intracellular pathways of ERK1, ERK2, Rela, Nrf-2, IkBkB, NFkB except CDC42, Akt1. In conclusion, two of the major pathways of hyperglycemia-induced organ damage were clearly activated within the testis of T1DM mice. This provides therapeutical opportunities in the treatment of diabetic male reproductive dysfunction. Nature Publishing Group UK 2019-09-10 /pmc/articles/PMC6736974/ /pubmed/31506549 http://dx.doi.org/10.1038/s41598-019-49600-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Maresch, Constanze C. Stute, Dina C. Fleming, Thomas Lin, Jihong Hammes, Hans-Peter Linn, Thomas Hyperglycemia induces spermatogenic disruption via major pathways of diabetes pathogenesis |
title | Hyperglycemia induces spermatogenic disruption via major pathways of diabetes pathogenesis |
title_full | Hyperglycemia induces spermatogenic disruption via major pathways of diabetes pathogenesis |
title_fullStr | Hyperglycemia induces spermatogenic disruption via major pathways of diabetes pathogenesis |
title_full_unstemmed | Hyperglycemia induces spermatogenic disruption via major pathways of diabetes pathogenesis |
title_short | Hyperglycemia induces spermatogenic disruption via major pathways of diabetes pathogenesis |
title_sort | hyperglycemia induces spermatogenic disruption via major pathways of diabetes pathogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736974/ https://www.ncbi.nlm.nih.gov/pubmed/31506549 http://dx.doi.org/10.1038/s41598-019-49600-4 |
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