• Philipps, Anthony F (PI)

Project: Research project

Project Details


Insulin is thought to be an important hormone in the regulation and control
of growth of the fetus of late gestation. Macrosomic infants borne to
diabetic women and growth retarded fetuses with absence of the pancreas
appear to offer naturally occuring instances of the effects of either
insulin excess or deficiency upon fetal growth. The goals of the proposed
work are: a) to define the metabolic and growth related effects of chronic
insulin secretory deficiency using both sheep and rabbit models of
intrauterine growth; b) to explore further the previously made observations
that fetal hyperglycemia induces a dramatic increase in fetal metabolic
rate and placental lactate production. In fetal lambs, glucose induced
changes in muscular work and cerebral metabolism and function will be
observed. In rabbits, the effects of chronic hyperglycemia upon fetal
growth, with particular emphasis upon fetal fat synthesis, will be studied;
c) the effects of superimposed asphyxia upon chronic fetal hyperglycemia
will be investigated to test the hypothesis that glucose induced increase
in fetal and fetal cerebral metabolic rate and in placental lactate
delivery to the fetus may place such fetuses at a great risk of hypoxia
induced white matter injury, the forerunners of cerebral palsy. In portion
a) fetal injection of streptozotocin into chronically catheterized fetal
lambs and fetal rabbits will be used to explore the relationship between
insulin secretory rate and umbilical substrate uptake and consequent fetal
growth. In portion b) chronic glucose infusions into either mothers
(rabbits) or fetuses (lambs) will be given to study fetal metabolic rate
changes and growth. In part c) using a fetal twin lamb model, the effects
of superimposed hypoxia in hyperglycemic and control lambs can be assessed
relative to histologic evidence of brain damage and correlated with both
fetal electroencephalography and cerebral lactate concentrations.
Effective start/end date6/1/7911/30/91


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)


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