title: Increased hepatic peroxisome proliferator-activated receptor coactivator-1α expression precedes the development of insulin resistance in offspring of rats from severe hyperglycemic mothers.
abstract: BACKGROUND
  Prenatal hyperglycaemia may increase metabolic syndrome susceptibility of the offspring. An underlying component of the development of these morbidities is hepatic gluconeogenic molecular dysfunction. We hypothesized that maternal hyperglycaemia will influence her offsprings hepatic peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) expression, a key regulator of glucose production in hepatocytes.
  
  
  METHODS
  We established maternal hyperglycaemia by streptozotocin injection to induce the maternal hyperglycaemic Wistar rat model. Offspring from the severe hyperglycemia group (SDO) and control group (CO) were monitored until 180 days after birth. Blood pressure, lipid metabolism indicators and insulin resistance (IR) were measured. Hepatic PGC-1α expression was analyzed by reverse transcription polymerase chain reaction and Western blotting. mRNA expression of two key enzymes in gluconeogenesis, glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK), were analyzed and compared.
  
  
  RESULTS
  In the SDO group, PGC-1α expression at protein and mRNA levels were increased, so were expression of G-6-Pase and PEPCK (P < 0.05). The above effects were seen prior to the onset of IR.
  
  
  CONCLUSIONS
  The hepatic gluconeogenic molecular dysfunction may contribute to the metabolic morbidities experienced by this population.
authors.affiliation: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
authors.forename: Jing-mei
authors.initials: JM
authors.lastname: Ma
authors.forename: Chan-juan
authors.initials: CJ
authors.lastname: Zeng
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Chong
authors.initials: C
authors.lastname: Shou
authors.forename: Hui-xia
authors.initials: HX
authors.lastname: Yang
mesh_terms: D000818:Animals; D005260:Female; D006943:Hyperglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016601:RNA-Binding Proteins; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity; D014157:Transcription Factors
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D013311:Streptozocin