Prevention of hypoinsulinemia modifies catecholamine effects in fetal sheep

Abstract

Increased epinephrine (Epi) and norepinephrine (NE) production plays an important role in fetal adaptation to reduced oxygen and/or nutrient availability, inhibiting insulin secretion and slowing growth to support more essential processes. To assess the importance of hypoinsulinemia for the efficacy of catecholamines, normoinsulinemia was restored by intravenous insulin infusion (0.18 mU ⋅ kg− 1 ⋅ min− 1) during prolonged infusion of either Epi (0.25–0.35 μg ⋅ kg− 1 ⋅ min− 1for 12 days, n = 7) or NE (0.5–0.7 μg ⋅ kg− 1 ⋅ min− 1for 7 days, n = 6) into normoxemic fetuses in twin-pregnant ewes, from 125–127 days of gestation. Insulin infusion for 8 days during Epi infusion or for 4 days during NE infusion decreased arterial blood pressure, O2 content, and plasma glucose, but increased heart rate significantly (all P <0.05), despite continuation of Epi or NE infusion. Cessation of insulin infusion reversed these changes. Estimated growth of fetuses infused with insulin during Epi or NE infusion (55 ± 13.9 and 83 ± 15.2 g/day) did not differ significantly from that of untreated controls (72 ± 15.4 g/day, n = 6). Growth of selected muscles and hindlimb bones was not altered either. Restoration of normoinsulinemia evidently counteracts the redistribution of metabolic activity and decreased anabolism brought about by Epi or NE in the fetus. Inhibition of insulin secretion by Epi and NE, therefore, appears essential for the efficacy of catecholamine action in the fetus.