Limited maternal fuel availability due to hyperinsulinemia retards fetal growth and development in the rat.
We rendered pregnant rats chronically hyperinsulinemic to determine the effect of reduced maternal metabolic fuel availability on fetal growth and development. We implanted osmotically driven insulin loaded minipumps on day 14 (term 21.5 days) in pregnant rats. This significantly increased maternal plasma concentrations of insulin and reduced glucose from day 15 until term. From day 17 until birth, fetal growth was significantly less for hyperinsulinemic mothers (term birth weight 4.53 +/- 0.07 versus 5.64 +/- 0.06 g, p less than 0.001). In fetuses of hyperinsulinemic mothers plasma glucose and insulin concentrations were significantly reduced while glucagon concentrations were increased. Total plasma amino acids were significantly reduced in maternal rats and their fetuses from days 17 to 19 while arteriovenous blood gas tensions and pH did not differ between fetuses of hyperinsulinemic and control mothers. Small for gestational age newborn pups of hyperinsulinemic mothers were hypoglycemic for the first 240 min of life as a result of limited hepatic glycogen stores and a delay in the normally expected induction of hepatic cytosolic phosphoenolpyruvate carboxykinase. This occurred despite significant increases in neonatal plasma glucagon concentrations. These data indicate that limitation of maternal glucose and amino acids with normal placental gaseous exchange retards fetal growth, limits hepatic glycogen deposition, and delays neonatal phosphoenolpyruvate carboxykinase induction. Limited fetal insulin secretion resulting from diminished maternal fuel availability may have also been a factor in retarding growth. The delay in phosphoenolpyruvate carboxykinase induction despite enhanced glucagon secretion during fetal and neonatal life suggests a specific "resistance" to this hormone in the rat growth retarded by limited metabolic fuel availability.
Ogata
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ES
Department of Pediatrics, Northwestern University Medical School, Northwestern Memorial Hospital, Chicago, Illinois.
Paul
R I
RI
Finley
S L
SL
D000596:Amino Acids / Q000097:blood*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology*; D005934:Glucagon / Q000097:blood; D006946:Hyperinsulinism / Q000150:complications / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007332:Insulin Infusion Systems; D008431:Maternal-Fetal Exchange; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D051381:Rats
D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D010729:Phosphoenolpyruvate Carboxykinase (GTP)