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


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.
International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.|Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
Yong
Y
Zhang
International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
Ying
Y
Zhang
International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
Guo-Lian
GL
Ding
International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
Xin-Mei
XM
Liu
Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
Jianping
J
Ye
Department of Pathophysiology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
Jian-Zhong
JZ
Sheng
International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
Jianxia
J
Fan
International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.|Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
He-Feng
HF
Huang
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D016640:Diabetes, Gestational / Q000503:physiopathology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D018149:Glucose Intolerance / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008297:Male; D051379:Mice; D010766:Phosphorylation; D011247:Pregnancy; D011773:Pyruvates / Q000378:metabolism
D001786:Blood Glucose; D011773:Pyruvates; D007658:Ketone Oxidoreductases; C053164:pyruvate dehydrogenase (NADP+)
gestational diabetes mellitus; glucose intolerance; offspring; phosphorylation; pyruvate dehydrogenase