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Hypoglycemia in the newborn growth-retarded rat: delayed phosphoenolpyruvate carboxykinase induction despite
Insights
Newborn small for gestational age (SGA) rat pups experience hypoglycemia due to low hepatic glycogen and impaired gluconeogenesis. Glucagon administration at birth helps normalize glucose levels by promoting PEPCK induction.
Area of Science:
- Perinatal physiology
- Neonatal adaptation
- Endocrinology
Background:
- Small for gestational age (SGA) neonates often exhibit metabolic disturbances.
- Hypoglycemia is a common complication in SGA infants, necessitating understanding of its underlying mechanisms.
Purpose of the Study:
- To investigate the metabolic changes in SGA rat pups during the early neonatal period.
- To elucidate the roles of hepatic glycogen, gluconeogenesis, and hormonal regulation in SGA hypoglycemia.
Main Methods:
- Characterization of plasma glucose, insulin, and glucagon levels in SGA and control rat pups.
- Measurement of hepatic glycogen and phosphoenolpyruvate carboxykinase (PEPCK) activity.
- Assessment of glucagon's effect on PEPCK induction and glucose levels in SGA pups.
Main Results:
- SGA pups exhibited reduced plasma glucose and hepatic glycogen stores at birth.
- Impaired induction of hepatic PEPCK activity was observed in SGA pups.
- Glucagon administration at birth corrected hypoglycemia and accelerated PEPCK induction in SGA pups.
Conclusions:
- Neonatal hypoglycemia in SGA pups results from depleted hepatic glycogen and impaired gluconeogenesis.
- Delayed PEPCK induction, potentially due to inadequate glucagon signaling, contributes to hypoglycemia in SGA neonates.
Abstract:
We have characterized the sequential changes in plasma glucose, insulin and glucagon concentrations, and hepatic glycogen and phosphoenolpyruvate carboxykinase (PEPCK) during the first 240 min of life in rat pups growth retarded [small for gestational age (SGA)] due to bilateral maternal uterine artery ligation. Pups of sham and nonoperated (normal) mothers served as controls. SGA pups were smaller, had reduced liver mass, and demonstrated a pattern of hypoglycemia. They had significantly reduced plasma glucose concentrations at birth, 20, and 240 min but had normal values at 60 and 120 min. SGA pups had significantly reduced hepatic glycogen stores at birth. Plasma glucagon concentrations in SGA pups increased significantly at 20 and 60 min while insulin concentrations decreased equally in all groups. Hepatic PEPCK activity increased greatly in the sham and normal pups. SGA pups did not induce PEPCK during the first 240 min of life; however, pharmacologic doses of glucagon at birth accelerated PEPCK induction in SGA pups and prevented hypoglycemia. These data indicate that newborn SGA pups develop hypoglycemia because of limited hepatic glycogen stores and retarded gluconeogenesis. The delay in PEPCK induction in SGA pups may result from an inadequate although increased glucagon release at birth or diminished sensitivity to available glucagon.