TRANSPORT OF INSULIN ACROSS THE BLOOD-BRAIN-BARRIER - SATURABILITY ATEUGLYCEMIC DOSES OF INSULIN

Blood borne insulin is known to cross the blood-brain barrier (BBB) wh ere it can act as a satiety peptide. We examined in mice the pharmacok inetics and characteristics of such passage by multiple-time regressio n analysis. The unidirectional influx constant (Ki) of human insulin r adioactively labeled with iodine (I-Ins) ranged from 0.87 to 1.7 mu l/ g-min. The transport of I-Ins was inhibited almost 50% by 0.1 mu g/mou se of unlabeled human insulin, a dose that had no effect on serum gluc ose. Similar results were found with rat insulin. The results with sel f-inhibition suggest that any hemoencephalic signal transmitted by the blood to brain transport of insulin is independent of the effects of insulin on glucose. The transport of I-Ins was altered by aluminum but not by administration of tyrosine, verapamil, or leptin, indicating i ndependence from amino acid transport, the p-glycoprotein system, a sl ow calcium channel, or leptin transport. By contrast with insulin, enz yme degradation limited the uptake and accumulation by brain of intrav enously injected, radioactively labeled glucagon and glucagon-like pep tide. In conclusion, these results are consistent with the view that i nsulin can affect satiety and related behaviors independently of its p eripheral effects by crossing the BBB to act within the brain. (C) 199 7 Elsevier Science Inc.