Insulin downregulates neonatal brain insulin receptors

Insulin (2U-regular) was administered intracerebrally or intraperitoneally in newborn rabbit pups, to study the effect of the hormone on brain insulin receptor characteristics. Intraperitoneal insulin treatment produced an increase in plasma insulin concentrations from a control of approximately 24 microU/ml to 132 +/- 36 (p less than 0.02) and a decrease in plasma glucose from approximately 83 to 27 +/- 10 mg/dl (p less than 0.01). No change in brain insulin receptor characteristics was observed. On the other hand, insulin injected intracerebrally raised the plasma insulin to greater than 3000 microU/ml and lowered the plasma glucose to 32 +/- 8 mg/dl (p less than .05). In addition a decrease in brain insulin receptor sites from 262 +/- 9 X 10(10) mg protein-1 to 159 +/- 6 (p less than 0.001) was noted. When the data was expressed per microgram DNA, a decrease from 4 +/- 0.4 X 10(10) to 2.5 +/- 0.2 (p less than .01) in receptor sites resulted. No change in the receptor affinity was observed. We conclude that a direct exposure of the brain to excess insulin results in a down-regulation of the brain insulin receptors.