This proposal focuses on portal vein gluocosensors. In previous studies by the investigator it has been shown that glucosensors in the portohepatic system were important for the sympathoadrenal response to hypoglycemia. More recently the presence of portohepatic glucosensors was localized to the portal vein. The investigation of the specific localization of these glucosensors will help to elucidate the underlying portal glucodetection. The preliminary findings indicate that intac portal innervation is essential to mounting a full sympathoadrenal response to hypoglycemia. In this proposal the investigator will employ variations of the """"""""local irrigation technique"""""""" to address the following specific aims: To elucidate the metabolic signals underlying glucose detection by the portal glucose-sensitive afferents. To delineate the neural pathway by which portal glucosensing is mediated. This will be accomplished by a series of selective nerve sectionings and chemical denervations serving to constrain the requisite neural pathway and nerve type. To ascertain the impact of the antecedent hypoglycemia upon the portal glucosensors. The sympathetic response to a hyperinsulinemic-hypoglycemic clamp in animals undergoing two prior days of hypoglycemic episodes will be compared with peripheral versus portal glucose infusion.
