Use of fetal streptozotocin injection to determine the role of normal levels of fetal insulin in regulating uteroplacental and umbilical glucose exchange.

Abstract

The present study was performed to determine the role of the normal fetal concentration of insulin in regulating placental-fetal glucose exchange. Fetal insulin deficiency was produced by streptozotocin injection into near term fetal sheep, and the effects of this insulin deficiency on net uteroplacental glucose uptake and net umbilical glucose uptake were measured. Each fetus received two or three doses of streptozotocin, 100 mg.kg-1.dose-1, given on separate days. This dosage of streptozotocin produced a 97.6% reduction in fetal pancreatic insulin content, a fall in fetal plasma insulin concentration (21 +/- 2 to 10 +/- 1 microU.ml-1), a rise in fetal plasma glucagon concentration (57 +/- 4 to 114 +/- 19 pg.ml-1), a rise in fetal blood glucose concentration (20.4 +/- 0.9 to 33.4 +/- 4.4 mg.dl-1), and a failure of insulin secretion in response to glucose infusion. Fetal blood oxygen content and umbilical oxygen uptake were normal and did not change during the entire study. Umbilical glucose uptake was reduced by 66% (5.98 +/- 0.38 to 2.02 +/- 1.31 mg.min-1.kg-1) after the streptozotocin-induced hypoinsulinemia and hyperglycemia but was returned to the control level by an insulin infusion into the fetus that reestablished the control maternal to fetal glucose concentration gradient. Net uteroplacental glucose uptake (consumption) did not change throughout the study. Because glucose concentration and umbilical glucose uptake could be normalized by an insulin infusion, it is unlikely that direct or toxic effects of streptozotocin on fetal or placental glucose metabolism were primarily responsible for the hyperglycemia and the reduced rate of umbilical glucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)