Effect of insulin on glucose uptake in near-term fetal lambs.

Glucose clamp experiments were performed in 27 chronically catheterized, late-gestation fetal lambs in order to measure the effect of fetal insulin concentration on fetal glucose uptake at a constant glucose concentration. Fetal arterial blood glucose concentration was measured over a 30-min control period and then maintained at the control value by a variable glucose infusion into the fetus while insulin was infused at a constant rate into the fetus. Plasma insulin concentration increased from 21 +/- 10 (SD) to 294 +/- 179 (SD) microU X ml-1. The exogenous glucose infusion rate necessary to maintain constant glycemia during the plateau hyperinsulinemia averaged 4.3 +/- 1.6 (SD) mg X min-1 X kg-1. In a subset of 13 animals, total fetal exogenous glucose uptake (FGU; sum of glucose uptake from the placenta via the umbilical circulation plus the steady-state exogenous glucose infusion rate) was measured during the control and hyperinsulinemia period. FGU was directly related to insulin concentration (y = 4.24 + 0.07x) at insulin levels less than 100 microU/ml and increased 132% above control at insulin levels above 100 microU/ml. Hyperinsulinemia did not affect fetal glucose uptake from the placenta via the umbilical circulation. These studies demonstrate that insulin concentration is a major factor controlling glucose uptake in the near-term fetal lamb, and that an increase of fetal insulin does not affect the transport of glucose to the fetus from the placenta.