IT HAS BEEN HYPOTHESIZED THAT INSULIN LEVELS OR BRAIN INSULIN KINETICS MAY BE INVOLVED IN AN INDIVIDUALS WEIGHT SET POINT. USING A TWO COMPARTMENT MODEL (CEREBROSPINAL FLUID [CSF]) AND AN INTERMEDIATE COMPARTMENT HYPOTHESIZED TO BE BRAIN INTERSTITIAL FLUID (ISF) WITH A FORCING FUNCTION REPRESENTING PLASMA INSULIN DRIVING THE SYSTEM, CSF INSULIN DATA IN DOGS WERE FITTED TO A MODEL TO DETERMINE INSULIN TRANSPORT RATE CONSTANTS INTO THE CENTRAL NERVOUS SYSTEM. USING THE THEORY OF OPTIMAL SAMPLING DEVELOPED BY RFKA, THE RATE CONSTANTS CHARACTERIZING THE MODEL WERE DETERMINED WITH EXCELLENT PRECISION; THE RESULTS SHOWED A SATURABLE TRANSPORT SYSTEM (MANUSCRIPT PUBLISHED IN J. CLIN. INVEST.). ANOTHER SET OF EXPERIMENTS SHOWED THE SYSTEM WAS SENSITIVE TO TREATMENT WITH DEXAMETHASONE, AND THAT SUCH TREATMENT DECREASED PLASMA INSULIN UPTAKE (MANUSCRIPT SUBMITTED TO DIABETES). THE FINAL SET OF EXPERIMENTS STUDIED OBESITY, AND FOUND THAT WITH WEIGHT GAIN PLASMA INSULIN UPTAKE CHANGED INDEPENDENTLY FROM THE OTHER MODEL PARAMETERS. IT IS HYPOTHESIZED AS A RESULT OF THESE STUDIES THAT INSULIN DELIVERY TO THE CNS IS A MAJOR PREDICTOR OF FOOD INTAKE AND BODY WEIGHT GAIN DURING HIGH FAT FEEDING IN DOGS (MANUSCRIPT TO BE SUBMITTED TO SCIENCE). DR. BAURA, WHO HAS LEFT THE UNIVERSITY FOR AN INDUSTRIAL POSITION, HAS CONTINUED TO DEVELOP THE THEORY, AND HAS PROPOSED A NONINVASIVE TECHNIQUE TO MEASURE INSULIN TRANSPORT IN THE CSF IN HUMANS. A PRELIMINARY PATENT HAS BEEN OBTAINED, AND SHE IS ACTIVELY SEEKING SUPPORT FROM THE PHARMACEUTICAL INDUSTRY TO CONTINUE HER WORK. IF SUCCESSFUL, A MAJOR NEW COLLABORATIVE EFFORT WILL COMMENCE AND SAAM II WILL BE THE DATA ANALYSIS TOOL OF CHOICE.
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