Characterization of Glucose Metabolism in the Isolated Rat Heart During Fetal and Early Neonatal Development

Abstract

Uptake of 1-14-C glucose, lactate production, 14-C-CO2 production, glycogen content, and the incorporation of 1-14-C glucose into glycogen, protein, and lipid have been studied in isolated fetal and neonatal rat hearts from the sixteenth day of gestation to the fifth neonatal day. The effects of insulin (5,000 μU./ml.) on these processes was also studied. Glucose uptake fell during gestation from 28.4 ± 2.2 to 10.0 ± 1.1 μmoles per gram wet weight tissue per two hours and remained constant after birth. At all ages insulin significantly increased glucose uptake. Lactate production Fell from 77.6 ± 11.5 to 51.5 ± 2.3 μmoles per gram wet weight per two hours between the sixteenth day of gestation and the first day after birth and was not influenced by insulin. Production of 14-C-CO2 from glucose was small (range: 2 to 7 per cent of glucose uptake) and was also unaffected by insulin. Hot KOH extractable cardiac glycogen content rose between the sixteenth and twenty-first day and then fell. The change in hot KOH extractable cardiac glycop; en followed similar changes in 1-14-C glucose incorporation into glycogen. Whereas 1-14-C glucose incorporation into tiot KOH extractable glycogen was unaltered by insulin until after birth, insulin did significantly augment the incorporation of 1-14-C glucose into the cold TCA extractable fraction. This fraction, which includes oligosaccharides destroyed by the hot KOH, also had a higher specific activity than the hot KOH extractable glycogen. The majority of the intracellular counts were in this fraction; the remainder of the counts were in the lactate and acetate or acetoacetate fraction. Insulin did not augment incorporation of 1-14-C glucose into these fractions. Incorporation of 1-14-C glucose into both protein and lipid was less than 2 per cent of glucose uptake and was not influenced by insulin. The data suggest that fetal myocardial development is characterized by a progressive decline in glucose uptake which can be stimulated by insulin from the sixteenth day onward. The conversion of 14-C glucose to 14-C-CO2, protein, and lipid was not influenced by insulin. Incorporation of 1-14-C glucose into hot KOH extractable glycogen was augmented by insulin only after birth under the experimental conditions described. The cold TCA extractable glycogen had a higher specific activity and insulin stimulated the incorporation of 1-14-C glucose into this fraction. It is concluded that insulin augments glucose uptake and incorporation into a glycogen fraction turning over rapidly in the fetal rat heart.