Control of fetal insulin secretion

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.