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 activity. Experiments were conducted in late gestation sheep fetuses prepared with chronic peripheral and adrenal catheters. The fetus mounted a brisk insulin response to hyperglycemia but with only a minimal change in the glucose-to-insulin ratio, indicating a tight coupling between insulin secretion and plasma glucose. In well-oxygenated fetuses, alpha(2)-adrenergic blockade by idazoxan effected no change in fetal insulin concentration, indicating the absence of a resting sympathetic inhibitory tone for insulin secretion. With hypoxia, fetal norepinephrine (NE) and epinephrine secretion and plasma NE increased markedly; fetal insulin secretion decreased strikingly with the degree of change related to extant plasma glucose concentration. Idazoxan blocked this effect showing the hypoxic inhibition of insulin secretion to be mediated by a specific alpha(2)-adrenergic mechanism. alpha(2)-Blockade in the presence of sympathetic activation secondary to hypoxic stress also revealed the presence of a potent beta-adrenergic stimulatory effect for insulin secretion. However, based on an analysis of data at the completion of the study, this beta-stimulatory mechanism was seen to be absent in all six fetuses that had been subjected to a prior experimentally induced hypoxic stress but in only one of nine fetuses not subjected to this perturbation. We speculate that severe hypoxic stress in the fetus may, at least in the short term, have a residual effect in suppressing the beta-adrenergic stimulatory mechanism for insulin secretion.
Jackson
B T
BT
Department of Surgery, Brown University School of Medicine, and the Providence Veterans Affairs Medical Center, Providence, Rhode Island 02908, USA. jackson.benjamin@providence.va.gov
Piasecki
G J
GJ
Cohn
H E
HE
Cohen
W R
WR
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002245:Carbon Dioxide / Q000097:blood; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D005333:Fetus / Q000502:physiology*; D005865:Gestational Age; D006706:Homeostasis; D006943:Hyperglycemia; D019329:Idazoxan / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D012756:Sheep
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D007328:Insulin; D002245:Carbon Dioxide; D010100:Oxygen; D009638:Norepinephrine; D019329:Idazoxan; D004837:Epinephrine