Medicine and Health Sciences Commons^™

Chronic Late-Gestation Hypoglycemia Upregulates Hepatic Pepck Associated With Increased Pgc1alpha Mrna And Phosphorylated Creb In Fetal Sheep., Paul J Rozance, Sean W Limesand, James S Barry, Laura D Brown, Stephanie R Thorn, Dan Loturco, Timothy Regnault, Jacob E Friedman, William W Hay

Paediatrics Publications

Hepatic glucose production is normally activated at birth but has been observed in response to experimental hypoglycemia in fetal sheep. The cellular basis for this process remains unknown. We determined the impact of 2 wk of fetal hypoglycemia during late gestation on enzymes responsible for hepatic gluconeogenesis, focusing on the insulin-signaling pathway, transcription factors, and coactivators that regulate gluconeogenesis. Hepatic phosphoenolpyruvate carboxykinase and glucose-6-phosphatase mRNA increased 12-fold and 7-fold, respectively, following chronic hypoglycemia with no change in hepatic glycogen. Chronic hypoglycemia decreased fetal plasma insulin with no change in glucagon but increased plasma cortisol 3.5-fold. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha mRNA …