[Increased expression of gluconeogenic enzymes in the liver of IUGR rats and subsequent insulin resistance].
OBJECTIVE
Intrauterine growth retardation (IUGR) is associated with insulin resistance in later life but the mechanism remains unclear. To explore the molecular mechanism of insulin resistance, we determined the expression of gluconeogenic enzymes as well as the expression of transcription factor which promotes gluconeogenesis in the liver of IUGR rats.


METHODS
Rat model of IUGR was established by maternal proteindouble ended arrowmalnutrition. Hepatic mRNA levels of the key enzymes for gluconeogenesis, PEPCK and G6Pase, and of peroxisome proliferator-activated receptor-gammacoactivator (PGC) -1alpha were measured by RT- PCR in male IUGR pup rats at 3 and 8 weeks of their lives. Hepatic PGC-1alpha protein levels were determined by Western blot.


RESULTS
The average birth weights of the IUGR group (4.97+/-0.83 g) were significantly lower than normal controls (6.54+/-0.52 g) (P<0.01). Until to 4 weeks of age, the weights of the IUGR rats increased to the control level and were higher than normal controls at 8 weeks of age (P<0.05). There were no significant differences in blood glucose and insulin concentrations between the IUGR rats and normal controls at 3 weeks of age. By 8 weeks of age, the IUGR rats showed high insulin concentrations (P<0.01) and high insulin resistance index (P<0.05) compared with the controls. Hepatic PGC-1alpha mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase in IUGR rats significantly increased at 3 and 8 weeks compared with controls.


CONCLUSIONS
An increased PGC-1alpha expression may contribute to increased mRNA levels of PEPCK and G6Pase, and thus induce the development of insulin resistance in later life in IUGR rats.
Liu
Xiao-Mei
XM
Central Laboratory, Shengjing Hospital, China Medical University, Shenyang 110004, China.
Lu
Yan
Y
Pan
Li-Li
LL
Li
Shu-Qin
SQ
D000818:Animals; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005943:Gluconeogenesis; D005952:Glucose-6-Phosphatase / Q000235:genetics; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology*; D008297:Male; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics
D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D005952:Glucose-6-Phosphatase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)