Impaired insulin secretion after intravenous glucose in neonatal rhesus monkeys that had been chronically hyperinsulinemic in utero.
Chronic hyperinsulinemia in the fetal rhesus monkey results in fetal macrosomia without change in fetal plasma glucose concentration. After 18 days of hyperinsulinemia, fetuses were delivered by cesarean section, at which time experimental animals had significantly (P less than 0.05) elevated umbilical artery plasma insulin concentrations of 2039 +/- 854 pM compared with 129 +/- 72 pM. Plasma immunoreactive C peptide (IRCP) was significantly reduced to 39 +/- 17 pM compared with 286 +/- 134 pM. Eight hours after the insulin-delivering pumps were removed, plasma glucose, insulin, and IRCP were the same in both the experimental and control groups. At this time, 0.5 g glucose/kg was given intravenously and insulin and IRCP secretion was measured over a 1-hr period. The secretion, as assessed by integrating the incremental response of both insulin and IRCP, was significantly (P less than 0.05) lower by 80% in the experimental animals compared with the controls. Our data show that experimentally produced in utero euglycemic hyperinsulinemia in the fetal rhesus monkey produces a defect in the glucose-mediated insulin secretory mechanism that is detectable in the neonatal period even when hyperinsulinemia is no longer present. This study provides more support for the concept that fuel/hormone-mediated fetal teratogenesis may explain some of the fetopathy of the infant of the diabetic mother.
Susa
J B
JB
Department of Pediatrics, Rhode Island Hospital, Brown University, Providence 02903.
Boylan
J M
JM
Sehgal
P
P
Schwartz
R
R
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D002908:Chronic Disease; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005315:Fetal Diseases / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008253:Macaca mulatta; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000150:complications
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005947:Glucose