Effects of Fetal Insulin Secretory Deficiency on Metabolism in Fetal Lamb

Fetal insulin secretion may be of importance in determining both fetal metabolic rate and glucose homeostasis in the resting state. To investigate this question, streptozocin (STZ) was injected into 10 late-gestation fetal lambs, and the effects of STZ on fetal pancreatic insulin storage and secretion, fetal metabolic rate, and umbilical glucose uptake were then studied. Fetal STZ injection caused a relative fetal hyperglycemia by 24 h after injection. Fetal hyperglycemia reached a maximum by 72 h and persisted for at least 10 days after injection. Neonates delivered after fetal injection were frankly diabetic. Fetal STZ injection was associated with complete suppression of both glucose- and tolbutamide-stimulated insulin release, although no changes in peripheral insulin concentration were observed when compared with controls. Fetal pancreatic insulin content was only 13% of that expected on the basis of gestational age. In a subgroup of 7 STZ-treated fetal lambs, fetal hyperglycemia was related to decrements in umbilical venoarterial difference of glucose, umbilical glucose uptake, and glucose-O₂ quotient. No changes in maternal glucose homeostasis or in fetal O₂ consumption were noted. The data suggest that deficient fetal insulin storage and secretion are associated with a decrement in exogenous fetal glucose entry but not in fetal metabolic rate. Whether the observed fetal changes relate to enhanced endogenous fetal glucoseproduction with a passive decrease in maternofetal glucose transfer or are simply due to a decrease in overall fetal glucose utilization is not known. It is speculated that a quantitative decrease in pancreatic insulin secretion is responsible for the observed changes.