Abstract
We investigated the downregulating effect of varying states (physiologic and pharmacologic) of systemic and intracranial hyperinsulinism on the 28 to 30 day fetal rabbit brain insulin receptor. Alloxan-induced maternal diabetes (n=5) produced mild fetal hyperinsulinemia (D) (plasma insulin concentrations = 59.80 ± 8.10 μU/ml, control = 26.25 ± 3.70; p < 0.01), whereas systemic administration (IMI) of 1.0 U (n=4) and 2.0 U (n=4) of insulin to the fetus resulted in moderate (103.13 ± 34.63 μU/ml) and severe (288.3 ± 51 μU/ml) fetal hyperinsulinemia respectively. All three states of systemic hyperinsulinemia neither altered the fetal brain insulin content nor the brain insulin receptor number and affinity. 0.01 U (n=4) of intracranial insulin administration (ICI) increased the brain insulin content four-fold (p < 0.01) but did not alter the brain insulin receptor number or affinity. 0.1 (n=5) and 2.0 U (n=7) of intracranial insulin increased the brain insulin content to supraphysiologic concentrations (p < 0.01) and decreased the fetal brain insulin receptor number (p < 0.01), the affinity remaining constant. We conclude that 1) regardless of the ability of insulin to cross the blood brain barrier, the downregulation of the brain insulin receptor is insulin dose-dependent and 2) the downregulation of the fetal brain insulin receptor is not a physiologic but a pharmacologic effect of insulin.
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