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Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia

AIM: Gestational diabetes mellitus (GDM) has been shown to be associated with a high risk of diabetes in offspring. In mitochondria, the inhibition of pyruvate dehydrogenase (PDH) activity by PDH phosphorylation is involved in the development of diabetes. We aimed to determine the role of PDH phosph...

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Autores principales: Zhang, Yong, Zhang, Ying, Ding, Guo-Lian, Liu, Xin-Mei, Ye, Jianping, Sheng, Jian-Zhong, Fan, Jianxia, Huang, He-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362479/
https://www.ncbi.nlm.nih.gov/pubmed/28148899
http://dx.doi.org/10.18632/oncotarget.14837
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author Zhang, Yong
Zhang, Ying
Ding, Guo-Lian
Liu, Xin-Mei
Ye, Jianping
Sheng, Jian-Zhong
Fan, Jianxia
Huang, He-Feng
author_facet Zhang, Yong
Zhang, Ying
Ding, Guo-Lian
Liu, Xin-Mei
Ye, Jianping
Sheng, Jian-Zhong
Fan, Jianxia
Huang, He-Feng
author_sort Zhang, Yong
collection PubMed
description AIM: Gestational diabetes mellitus (GDM) has been shown to be associated with a high risk of diabetes in offspring. In mitochondria, the inhibition of pyruvate dehydrogenase (PDH) activity by PDH phosphorylation is involved in the development of diabetes. We aimed to determine the role of PDH phosphorylation in the liver in GDM-induced offspring glucose intolerance. RESULTS: PDH phosphorylation was increased in lymphocytes from the umbilical cord blood of the GDM patients and in high glucose-treated hepatic cells. Both the male and female offspring from GDM mice had elevated liver weights and glucose intolerance. Further, PDH phosphorylation was increased in the livers of both the male and female offspring from GDM mice, and elevated acetylation may have contributed to this increased phosphorylation. MATERIALS AND METHODS: We obtained lymphocytes from umbilical cord blood collected from both normal and GDM pregnant women. In addition, we obtained the offspring of streptozotocin-induced GDM female pregnant mice. The glucose tolerance test was performed to assess glucose tolerance in the offspring. Further, Western blotting was conducted to detect changes in protein levels. CONCLUSIONS: Intrauterine hyperglycemia induced offspring glucose intolerance by inhibiting PDH activity, along with increased PDH phosphorylation in the liver, and this effect might be mediated by enhanced mitochondrial protein acetylation.
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spelling pubmed-53624792017-04-24 Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia Zhang, Yong Zhang, Ying Ding, Guo-Lian Liu, Xin-Mei Ye, Jianping Sheng, Jian-Zhong Fan, Jianxia Huang, He-Feng Oncotarget Research Paper AIM: Gestational diabetes mellitus (GDM) has been shown to be associated with a high risk of diabetes in offspring. In mitochondria, the inhibition of pyruvate dehydrogenase (PDH) activity by PDH phosphorylation is involved in the development of diabetes. We aimed to determine the role of PDH phosphorylation in the liver in GDM-induced offspring glucose intolerance. RESULTS: PDH phosphorylation was increased in lymphocytes from the umbilical cord blood of the GDM patients and in high glucose-treated hepatic cells. Both the male and female offspring from GDM mice had elevated liver weights and glucose intolerance. Further, PDH phosphorylation was increased in the livers of both the male and female offspring from GDM mice, and elevated acetylation may have contributed to this increased phosphorylation. MATERIALS AND METHODS: We obtained lymphocytes from umbilical cord blood collected from both normal and GDM pregnant women. In addition, we obtained the offspring of streptozotocin-induced GDM female pregnant mice. The glucose tolerance test was performed to assess glucose tolerance in the offspring. Further, Western blotting was conducted to detect changes in protein levels. CONCLUSIONS: Intrauterine hyperglycemia induced offspring glucose intolerance by inhibiting PDH activity, along with increased PDH phosphorylation in the liver, and this effect might be mediated by enhanced mitochondrial protein acetylation. Impact Journals LLC 2017-01-27 /pmc/articles/PMC5362479/ /pubmed/28148899 http://dx.doi.org/10.18632/oncotarget.14837 Text en Copyright: © 2017 Zhang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhang, Yong
Zhang, Ying
Ding, Guo-Lian
Liu, Xin-Mei
Ye, Jianping
Sheng, Jian-Zhong
Fan, Jianxia
Huang, He-Feng
Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia
title Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia
title_full Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia
title_fullStr Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia
title_full_unstemmed Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia
title_short Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia
title_sort regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362479/
https://www.ncbi.nlm.nih.gov/pubmed/28148899
http://dx.doi.org/10.18632/oncotarget.14837
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