The newborn of diabetic rat. I. Hormonal and metabolic changes in the postnatal period.

Abstract

Summary: In this study we investigated the effects of streptozotocin-induced maternal diabetes on fetal body weight and alterations in the plasma concentrations of glucose, insulin, glucagon and catecholamines, and in the concentrations of pancreatic insulin and glucagon and of hepatic glycogen and cAMP in newborn rats during the first 6 h of life. Hyperglycemia was regulated in one group of diabetic pregnant rats by administration of insulin twice a day from day 18 of gestation. On day 22 of gestation the body weight of newborns of the insulin-treated diabetic rats was significantly higher than that of normal rats, whereas untreated maternal diabetes caused a reduction in the body weight of the newborns. The newborns of insulin-treated diabetic rats maintained lower concentrations of plasma glucose for a longer period compared to the age-matched neonates of normal rats. At birth and during the first 6 postnatal h of life, plasma insulin was significantly higher in the neonates of both treated and untreated diabetic rats than the age-matched pups of normal rats. There was an increase in the concentration of plasma pancreatic glucagon in the newborns of normal rats within 30 min after birth, in contrast, a gradual reduction or no change in the concentrations of plasma glucagon was observed in the neonates of both groups of diabetic rats during the 6 h postnatal period. The concentrations of plasma epinephrine and norepinephrine were very high at birth in the three groups of newborns, and declined rapidly during the first postnatal h. Significant secondary increases in the concentrations of these two hormones occurred in the three groups of neonates after the plasma glucose concentration had declined to below 2 mM. Changes in the insulin:glucagon molar ratio was associated with a delay in the postnatal increase in hepatic cAMP concentrations and also in the initiation of hepatic glycogenolysis in the neonates of both groups of diabetic rats compared to normal animals. The findings of macrosomia, postnatal hyperinsulinemia, prolonged lowered plasma glucose and attenuated plasma glucagon observed in the newborns of the insulin-treated diabetic rats are similar to the findings reported in the newborn infants of insulin-dependent diabetic women. Speculation: Diabetes during pregnancy in the rats described in this study is reproducible and can be regulated with insulin administration. This experimental model should prove useful in quantifying alterations in hepatic glycogen metabolism and gluconeogenesis, and the mechanism(s) responsible for the attenuated glucagon secretory response in newborns of diabetic mothers.