Pretreatment with glucose increases entry of urocortin into mouse brain

Although urocortin is a potent inhibitor of food ingestion after peripheral administration. it was recently shown that under normal conditions this pe ptide crosses the blood-brain barrier (BBB) at a very slow rate. We examine d whether hyperglycemia could stimulate the rate of entry (K-i) of I-125-ur ocortin into the mouse brain. In euglycemic mice, I-125-urocortin injected iv entered the brain at a rate similar to that of the vascular marker Tc-99 m-albumin. However, injection of glucose (3 g/kg, ip) 0.5, 1, or 2 h before the I-125-urocortin greatly increased the influx of urocortin. Without the glucose, the self-inhibition characteristic of a saturable transport syste m was not apparent. Self-inhibition could be demonstrated after the glucose injection, indicating activation of a transport system for urocortin that was saturable. Injection of insulin (10 U/kg, ip) 1 or 2 h before the I-125 -urocortin decreased the K-i. Thus, the entry of urocortin into brain can b e activated by changes in the concentration of blood glucose, illustrating the responsiveness of the BBB to regulatory influences. (C) 2001 Elsevier S cience Inc. All rights reserved.