Insulin resistance of gluconeogenic pathways in neonatal rats after prenatal ethanol exposure.
Alcohol exposure during pregnancy is associated with fetal growth restriction and programs the offspring to insulin resistance later in life. The underlying mechanisms are still uncertain, but a dysregulation of gluconeogenesis and adipose hormones may be contributory. Newborn rats from dams that had been given ethanol (EtOH) or water (controls) during pregnancy were studied. Adiponectin mRNA was determined in subcutaneous fat by RT-PCR, and serum adiponectin was measured by RIA. Subsets of rats were killed before and after intraperitoneal administration of insulin, to determine, by RT-PCR, the hepatic expression of gluconeogenic enzymes and that of the transcription factor peroxisome proliferator-activated receptor-coactivator (PGC)-1, which promotes gluconeogenesis. EtOH offspring had delayed hypoglycemic response to insulin but normal adiponectin mRNA and serum levels compared with controls. The inhibitory response of the gluconeogenic enzyme phosphoenol- pyruvate carboxykinase (PEPCK) and PGC-1 mRNAs to insulin was blunted in EtOH offspring compared with controls. The data suggest that intrauterine EtOH exposure causes insulin resistance of genes for PGC-1 and PEPCK early in life.
Chen
Li
L
Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3A1R9.
Zhang
Tong
T
Nyomba
B L G
BL
D052242:Adiponectin; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001724:Birth Weight / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000235:genetics / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000096:biosynthesis / Q000235:genetics; D011247:Pregnancy; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D052242:Adiponectin; D001786:Blood Glucose; D002492:Central Nervous System Depressants; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D000431:Ethanol; D024981:Glycogen Phosphorylase; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose