Fetal and Neonatal Metabolism in the Pup of a Canine Diabetic Mother: Hepatic Intermediary Metabolism

Abstract

The intrahepatic metabolic profile of pups from a diabetic canine pregnancy (IDM pups) was examined at birth and during the postnatal adaptation to 3, 6, 9 or 24 h of neonatal fasting. Hepatic intermediates of the glycogen, glycolytic, and Krebs cycles were determined in addition to hepatic adenine nucleotides and hepatic and muscle triglyceride concentrations. Maternal canine diabetes enhanced fetal hepatic and muscle glycogen and triglyceride content. After birth, neonatal hepatic glycogen content declined among control and IDM pups but glycogen content remained enhanced in the IDM pups at 3 and 6 h. Muscle glycogen also declined in both groups; however, it remained higher in the IDM at 3, 6, and 9 h. Muscle and hepatic triglyceride content increased in both groups. Postnatal intracellular triglyceride content was augmented in muscle tissue of the IDM at 3, 6, and 9 h while hepatic tissue from IDM had increased triglycerides at 24 h of age. Glycolytic intermediates demonstrated alterations following maternal diabetes as fructose 1, 6, diphosphate was lower in IDM pups during fetal life and at 3, 9, and 24 h while pyruvate and oxaloacetate concentrations were augmented throughout the study period when compared with age-matched controls. Hepatic amino acids demonstrated elevated alanine concentrations in IDM pup at 6, 9, and 24 h while aspartate levels were augmented during fetal and at 6, 9, and 24 h of neonatal fasting. These data suggest that hepatic glycogen synthesis is augmented in the fetus of the diabetic canine mother. After birth postnatal glycogenolysis is not altered and may support hepatic and systemic oxidative metabolism. Furthermore, these large tissue stores of glucose may contribute to hepatic or muscle triglyceride synthesis in addition to hepatic amino acid accumulation. The alterations of FDP, pyruvate, and oxaloacetic acid suggests that glycolysis is enhanced among pups following a diabetic pregnancy while intraheptic gluconeogenesis may be attenuated.