• Philipps, Anthony F (PI)

Project: Research project

Project Details


The proposed project is designed to ascertain specific questions related to
the modulation of substrate utilization and growth of the fetus and neonate
by the hormone insulin. The majority of the proposal will utilize the
chronically catherized fetal sheep as a model of fetal metabolism and
growth. The human fetus and infant of the pregnant diabetic may represent
a model for the effects of substrate surfeit and endogenous hyperinsulinism
upon fetal metabolism. To test the hypothesis that it is the fetal
hyperglycemia that induces altered insulin storage and macrosomia, chronic
fetal glucose infusions will be performed in one of twin fetal lambs and
the effects of infusion upon growth noted. Chronic epxerimental fetal
hyperglycemia causes a significant fetal hypoxemia which may be important
in gaining an understanding of the mechanisms behind the increased risks of
late fetal demise, neurologic impairment and polycythemia seen in some
fetuses of diabetic women. Oxygen consumption by uterus-placenta and
fetus, hypothesized to rise during hyperglycemic states, will be monitored
during glucose infusions in singleton fetal lambs. Effects of glucose vs.
fetal hyperinsulinism upon oxygen consumption may be able to be separated
using short term fetal infusions of somatostatin to suppress insulin
release during fetal hyperglycemia. Insulin may also play a role in
altering fetal uptake of amino acids and, therefore, protein synthesis.
Using controlled fetal lamb insulin infusions we wish to show that marked
fetal hyperinsulinism causes an increase in fetal uptake of amino acids
destined for use as fuel and/or protein accretion. Lastly, the role of
insulin in modulation of substrates in the neonate, particularly the low
birth weight premature infant, is unknown. Because of the limitations of
blood sampling in these tiny newborns, we wish to devlop an indirect
estimate of insulin release to assess further insulin's role in promoting
growth and also as a bioassay to assess adequacy of nutritional intake in
these babies. A small but measurable fraction of blood insulin is excreted
unchanged in the urine and can be measured easily in both adult and
neonate. By assessing urinary insulin excretion in the premature infant
and correcting for varying degrees of renal maturation, we hope to show
that increasing caloric intake and weight gain are associated with
increasing insulin excretion.
Effective start/end date6/1/797/31/86


  • National Institutes of Health


  • Medicine(all)


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