Bt. Jackson et al., HYPOXIA-INDUCED SYMPATHETIC INHIBITION OF THE FETAL PLASMA-INSULIN RESPONSE TO HYPERGLYCEMIA, Diabetes, 42(11), 1993, pp. 1621-1625
Citations number
22
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Large-for-delivery date babies, considered characteristic of diabetic
pregnancy, are believed to result from fetal hyperinsulinemia. Paradox
ically, infant birth weights tend to be low-for-delivery date in mothe
rs 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 a
nd adrenal cannulas. Fetal blood gases, lactate, norepinephrine, and e
pinephrine secretion rates; and plasma norepinephrine, glucose, and im
munoreactive insulin concentrations were determined at 30-min interval
s during a 2-h baseline period and a 4-h period of hyperglycemia divid
ed into 2-h segments of hypoxemia (with and without alpha-blockade) an
d 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, no
repinephrine and epinephrine secretion were elevated and the insulin r
esponse was blocked. With hypoxemia and phentolamine blockade, the ins
ulin response was enhanced with a 10-fold increase above baseline. In
severe maternal diabetes with vascular disease or with poor control an
d very high glucose levels, the fetus is likely to be relatively hypox
emic. Our experiments suggest that in this situation, the fetal insuli
n response to hyperglycemia will be attenuated; this effect is mediate
d, at least partly, through sympathoadrenal stimulation.