Fuels, Hormones, and Liver Metabolism at Term and during the Early Postnatal Period in the Rat

Abstract

A B ST R A C T The metabolic response to the first fast experienced by all mammals has been studied in the newborn rat. Levels of fuels and hormones have been compared in the fetal and maternal circulations at term. Then, after cesarean section just before the normal time of birth, sequential changes in the same parameters were quantified during the first 16 h of the neonatal period. No caloric intake was permitted, and the newborns were maintained at 370C. Activities of three key hepatic enzymes involved in glucose production were estimated.Marked differences in maternal and fetal hormones and fuels were observed. Lower levels of glucose, free fatty acids, and glycerol but higher levels of lactate, a-amino nitrogen, alanine, and glutamine were present in the fetus. Pyruvate, glutamate, and ketone bodies were not significantly different. The combination of a strikingly higher fetal immunoreactive insulin and a slightly lower immunoreactive glucagon (pancreatic) resulted in a profound elevation in the insulin-to-glucagon ratio, a finding consistent with an organism in an anabolic state.The rat at birth presents a body composition with respect to fuels available for mobilization and conversion which is dominated by carbohydrate and protein, since little fat is present. However, at birth a transient period of hypoglycemia occurred, associated with a rapid fall in insulin and rise in glucagon, causing reversal of the insulin-to-glucagon relationship toward ratios such as were observed in the mother. After a lag period, hepatic activities of phosphorylase, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase increased. Concurrent with these enzyme changes, the blood glucose returned to levels at or above those of the fetus. Interestingly, the fall observed in levels of the gluconeogenic precursors, lactate and amino acids, preceded the rise in enzyme activities and restoration of blood glucose. After 4 h, however, hypoglycemia recurred, during a period of decreasing hepatic glycogen content and blood lactate, pyruvate, and glycerol levels but of stable or increasing amino acid concentrations. Hepatic gluconeogenesis in this phase of depleted glycogen stores was insufficient to maintain euglycemia.Substrates derived from fat showed early changes of smaller magnitude. The rise in free fatty acids which occurred was less than twofold the value at birth, though this rise persisted up to 6 h. Whereas glycerol rose transiently, acetoacetate did not change and P-hydroxybutyrate concentration fell. Both ketone bodies showed a marked rise at 16 h, at a time of diminished free fatty acid levels. Plasma growth hormone, though higher in the fetal than the maternal circulation, showed no consistent change during the period of observation.The changes in levels of the endocrine pancreatic hormones at birth were appropriate in time, magnitude, and direction to be implicated as prime regulators of the metabolic response during the neonatal period in the rat.

The development of ketogenesis at birth in the rat

“…The pattern of change in blood ketone-body concentrations with time in the unfed pups (see Fig. 5) differs from that previously published by us (Girard et al, 1973). Ketone-body concentrations are higher for the first 6h after birth in the present study, but are lower at 16h.…”

“…for six to ten determinations. birth (Girard et al, 1973;Snell & Walker, 1973). The delivery of the whole litter in the rat lasts 1-2h.…”

“…The techniques used for collection of blood samples and the treatment of blood or plasma for assay of metabolites have been described previously (Girard et al, 1973).…”

“…Plasma non-esterified fatty acids were determined with radioactive nickel by the method of Ho (1970). Acetoacetate and 3-hydroxybutyrate were measured with a fluorimetric adaptation (Girard et al, 1973) …”

“…The rats were from an albino Wistar strain; gestational age was determined as described previously (Girard et al, 1973). The time of delivery of the pups born naturally was determined by carefully checking the appearance of the first and the last pup of the litter in the cage.…”