In this study, we investigated the way in which fetal insulin secretion is
influenced by interrelated changes in blood glucose and sympathoadrenal act
ivity. Experiments were conducted in late gestation sheep fetuses prepared
with chronic peripheral and adrenal catheters. The fetus mounted a brisk in
sulin response to hyperglycemia but with only a minimal change in the gluco
se-to-insulin ratio, indicating a tight coupling between insulin secretion
and plasma glucose. In well-oxygenated fetuses, alpha (2)-adrenergic blocka
de by idazoxan effected no change in fetal insulin concentration, indicatin
g the absence of a resting sympathetic inhibitory tone for insulin secretio
n. With hypoxia, fetal norepinephrine (NE) and epinephrine secretion and pl
asma NE increased markedly; fetal insulin secretion decreased strikingly wi
th the degree of change related to extant plasma glucose concentration. Ida
zoxan blocked this effect showing the hypoxic inhibition of insulin secreti
on to be mediated by a specific alpha (2)-adrenergic mechanism. alpha (2)-B
lockade in the presence of sympathetic activation secondary to hypoxic stre
ss also revealed the presence of a potent beta -adrenergic stimulatory effe
ct for insulin secretion. However, based on an analysis of data at the comp
letion of the study, this beta -stimulatory mechanism was seen to be absent
in all six fetuses that had been subjected to a prior experimentally induc
ed hypoxic stress but in only one of nine fetuses not subjected to this per
turbation. We speculate that severe hypoxic stress in the fetus may, at lea
st in the short term, have a residual effect in suppressing the beta -adren
ergic stimulatory mechanism for insulin secretion.