Persistence of impaired insulin secretion in infant rhesus monkeys that had been hyperinsulinemic in utero.
Chronic in utero hyperinsulinemia in the fetal rhesus monkey produces a number of changes in the fetus that are similar to those found in the human infant of the diabetic mother, including macrosomia, selective organomegaly, and altered insulin secretion during the neonatal period. The chronically hyperinsulinemic fetal rhesus model has been used to test the hypothesis that the effects of chronic hyperinsulinemia persist beyond the neonatal period into later life and may, in part, be responsible for the increased prevalence of impaired glucose tolerance or diabetes found in the human infant of the diabetic mother. We report that infant rhesus monkeys that had plasma insulin concentrations of approximately 10 times basal levels (2176 +/- 808 pmol compared to 172 +/- 101 pmol) exhibited reduced insulin secretion during the first 5 months of life. The integrated incremental change in plasma insulin and immunoreactive C-peptide (IRCP) concentration was significantly reduced by approximately 50% in response to i.v. glucose, arginine, and tolbutamide when given at 3, 4, and 5 months of age. The response to glucagon at 2 months of age was equivocal with a significantly reduced insulin response but without the corresponding IRCP reduction. There was no difference between groups in insulin sensitivity as measured at 6 months of age by an i.v. insulin tolerance test. The glucagon and glucose tolerance tests were repeated annually in both groups until the animals were 3 yr of age with no differences in insulin or IRCP secretion being observed. We conclude that chronic in utero euglycemic hyperinsulinemia results in impaired insulin secretion that persists beyond the neonatal period.
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; D001835:Body Weight; D002096:C-Peptide / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005315:Fetal Diseases / Q000097:blood*; D005320:Fetal Macrosomia / Q000209:etiology; D005865:Gestational Age; D006946:Hyperinsulinism / Q000097:blood* / Q000150:complications; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008253:Macaca mulatta; D011247:Pregnancy; D014469:Umbilical Arteries; D014471:Umbilical Veins
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin