1712 A PRIMATE MODEL FOR THE STUDY OF FETAL LUNG DEVELOPMENT IN THE GLUCOSE INTOLERANT PREGNANCY

Abstract

A procedure which reliably produces an insulin dependent state of glucose intolerance in Macaca mulatta is described, along with normal glucose disappearance rates(K) in adult female macaques and biochemical and physiologic indices of fetal lung development(FLD) in 3 diabetic progeny(IDM) and 5 matched controls. After an initial observation period and an IV glucose tolerance test, female monkeys received 47.5mg/kg of freshly mixed streptozotocin by rapid central intravenous injection. Subsequently the mean glucose disappearance rate was markedly decreased from 5.63±1.36% per min to 1.30±0.52% per min(P<.001) and no insulin response could be demonstrated. Fasting plasma glucose values averaged 245mg/dl and glycosylated hemoglobin levels were markedly elevated(x=14.7%). Urine volume was increased from 236±99ml/day to 1261±264ml/day(P<.001)and urine glucose from 10±3mg/dl/day to 4237±608mg/dl/day(P<.001). Lung biochemical analyses including phosphatidylcholine(PC) and phosphatidylglycerol(PG) are represented below(per gram wet wt) for fetuses delivered by C-section at 145 days gestation(term =165±3days). PG was not demonstrable in any of the 7 amniotic fluid samples analyzed and other lung indices (ie %V₁₀, Vmax,γmin) did not vary significantly from controls. Weights for IDM were strikingly abnormal at 629, 529 and 341 gms vs 390±19 gms for controls. Mean maternal/fetal plasma glucose values at birth were 203/147 mg/dl for diabetics and 45739 mg/dl for controls. In this pilot study, fetal animals with somatic features of IDM and altered FLD compared to controls were obtained. Therefore, this model provides an apt homologue for human diabetes.

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