Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1782516958946656256 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5362479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhangyong regulationofhepaticpyruvatedehydrogenasephosphorylationinoffspringglucoseintoleranceinducedbyintrauterinehyperglycemia AT zhangying regulationofhepaticpyruvatedehydrogenasephosphorylationinoffspringglucoseintoleranceinducedbyintrauterinehyperglycemia AT dingguolian regulationofhepaticpyruvatedehydrogenasephosphorylationinoffspringglucoseintoleranceinducedbyintrauterinehyperglycemia AT liuxinmei regulationofhepaticpyruvatedehydrogenasephosphorylationinoffspringglucoseintoleranceinducedbyintrauterinehyperglycemia AT yejianping regulationofhepaticpyruvatedehydrogenasephosphorylationinoffspringglucoseintoleranceinducedbyintrauterinehyperglycemia AT shengjianzhong regulationofhepaticpyruvatedehydrogenasephosphorylationinoffspringglucoseintoleranceinducedbyintrauterinehyperglycemia AT fanjianxia regulationofhepaticpyruvatedehydrogenasephosphorylationinoffspringglucoseintoleranceinducedbyintrauterinehyperglycemia AT huanghefeng regulationofhepaticpyruvatedehydrogenasephosphorylationinoffspringglucoseintoleranceinducedbyintrauterinehyperglycemia |