The fetal heart insulin receptor responds differently to varying plasma insulin concentrations.

We investigated in vivo the effect of varying plasma concentrations of insulin on the 28- and 30-day-old fetal rabbit heart insulin receptors using plasma membranes. Alloxan induced maternal diabetes (n = 5) associated with fetal hyperglycemia and mild hyperinsulinemia (59.80 +/- 8.10 microU/ml versus a control of 26.25 +/- 3.70, p less than 0.01) increased the insulin receptor number from a control (30 d) of 168 +/- 1.01 to 320 +/- 34 X 10(10)/mg protein (p less than 0.01). Fetal administration of 1.0 U of insulin (n = 4) resulting in normoglycemia and moderately high plasma insulin concentrations (103.3 +/- 34.63 microU/ml versus a control of 13.72 +/- 1.60, p less than 0.05) did not alter the insulin receptor number (28 d). On the other hand fetal administration of 2.0 U of insulin (n = 4) resulting in hypoglycemia and severely high plasma insulin concentrations (288.3 +/- 51 microU/ml versus a control of 13.72 +/- 1.60, p less than 0.01) decreased the insulin receptor number from a control (28 d) of 200 +/- 23 to 82 +/- 23 X 10(10)/mg protein (p less than 0.01). The receptor affinity remained constant. We conclude that the downregulation (decrease) of the fetal heart insulin receptors in vivo is not a physiologic but a pharmacologic effect of insulin.