An experimental model for studies of fetal maldevelopment in the diabetic pregnancy

Abstract

Values for plasma glucose and serum insulin in fasting conditions and glucose disappearance rates during an intravenous glucose tolerance test were obtained from 54 adult female rhesus monkeys. Some of these animals were subsequently made diabetic by intravenous infusion of streptozotocin (STZ). A single treatment with STZ (47.5 mg/kg) was consistently effective in ten animals for inducing severe hyperglycemia and diminished insulin response to glucose infusion. One of four additional animals became significantly glucose intolerant after a single treatment with STZ (30 mg/kg) and three of three animals became glucose intolerant after two treatments at this dosage. The greater effectiveness of STZ for inducing severe diabetes mellitus in the present study compared with previous investigations using nonhuman primates was attributed to rapid mixing and infusion of STZ with proven diabetogenic activity. Severely diabetic animals have been successfully maintained by daily subcutaneous injections of a combination of NPH and regular insulin. Fetuses of monkeys treated with STZ before conception were hyperglycemic and hyperinsulinemic, and four of these six fetuses were large for gestational age. Preliminary data suggest that fetal lung glycogen concentrations were elevated in these animals compared with controls at 145 days of gestation. It is concluded that the rhesus monkey treated with STZ before pregnancy represents a useful model for studies of fetal maldevelopment in pregnancies complicated by varying degrees of maternal diabetes.