Hypoxia-induced sympathetic inhibition of the fetal plasma insulin response to hyperglycemia.
Large-for-delivery date babies, considered characteristic of diabetic pregnancy, are believed to result from fetal hyperinsulinemia. Paradoxically, infant birth weights tend to be low-for-delivery date in mothers with more severe diabetes. We tested the hypothesis that hypoxemia in such fetuses leads to sympathoadrenal stimulation and inhibition of insulin secretion; and, thus, produces a net reduction in the growth-promoting effects. Fetal sheep were prepared with chronic peripheral and adrenal cannulas. Fetal blood gases, lactate, norepinephrine, and epinephrine secretion rates; and plasma norepinephrine, glucose, and immunoreactive insulin concentrations were determined at 30-min intervals during a 2-h baseline period and a 4-h period of hyperglycemia divided into 2-h segments of hypoxemia (with and without alpha-blockade) and hyperoxia. Hypoxemia-hyperoxia sequences were varied randomly. Well-oxygenated fetuses responded to a threefold increase in glucose with a sixfold increase in plasma immunoreactive insulin. With hypoxemia, norepinephrine and epinephrine secretion were elevated and the insulin response was blocked. With hypoxemia and phentolamine blockade, the insulin response was enhanced with a 10-fold increase above baseline. In severe maternal diabetes with vascular disease or with poor control and very high glucose levels, the fetus is likely to be relatively hypoxemic. Our experiments suggest that in this situation, the fetal insulin response to hyperglycemia will be attenuated; this effect is mediated, at least partly, through sympathoadrenal stimulation.
Jackson
B T
BT
Department of Surgery, Brown University, Providence, Rhode Island.
Cohn
H E
HE
Morrison
S H
SH
Baker
R M
RM
Piasecki
G J
GJ
D000818:Animals; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000032:analysis; D004195:Disease Models, Animal; D004837:Epinephrine / Q000097:blood; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000502:physiology*; D007003:Hypoglycemia / Q000097:blood* / Q000503:physiopathology*; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000097:blood*; D007773:Lactates / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D011247:Pregnancy; D012756:Sheep / Q000097:blood / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D009638:Norepinephrine; D004837:Epinephrine