Oncotarget

Research Papers:

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

Yong Zhang, Ying Zhang, Guo-Lian Ding, Xin-Mei Liu, Jianping Ye, Jian-Zhong Sheng, Jianxia Fan and He-Feng Huang _

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Oncotarget. 2017; 8:15205-15212. https://doi.org/10.18632/oncotarget.14837

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Abstract

Yong Zhang1,2,*, Ying Zhang1,*, Guo-Lian Ding1, Xin-Mei Liu1, Jianping Ye3, Jian-Zhong Sheng4, Jianxia Fan1,*, He-Feng Huang1,2,*

1International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China

2Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China

3Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA

4Department of Pathophysiology, School of Medicine, Zhejiang University, Hangzhou 310058, China

*These authors contributed equally to this work

Correspondence to:

He-Feng Huang, email: [email protected]

Jianxia Fan, email: [email protected]

Keywords: gestational diabetes mellitus, offspring, pyruvate dehydrogenase, glucose intolerance, phosphorylation

Received: December 01, 2016     Accepted: January 11, 2017     Published: January 27, 2017

ABSTRACT

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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