Characterization of neural mechanisms involved in hypoglycemic detection at the portal vein.

摘要

Portal glucose sensors play a critical role in hypoglycemic detection and the subsequent sympathoadrenal response. However, the specific neural pathway and type of neuron responsible for mediating the afferent signal has not been elucidated. Further, the impact of antecedent hypoglycemia (known to suppress counterregulation) upon portal glucose sensing remains unknown. In the current dissertation, experiments were conducted addressing three specific aims, (A) to clarify the neural pathway by which the afferent signal from the portal glucose sensors is mediated, (B) to investigate the specific nerve type involved in the portal glucose sensing, and (C) to assess the impact of antecedent hypoglycemia on portal glucose sensing.; In Experiment A, male Wistar rats underwent either hepatic vagotomy (HV), total subdiaphragmatic vagotomy (TSV) or celiac ganglionectomy (CG). When exposed to systemic hypoglycemia (2.58mM) a week later, CG animals demonstrated a 30% to 50% suppression in the sypathoadrenal response. In contrast, HV and TSV animals demonstrated normal responses.; In Experiment B, capsaicin was applied topically to the portal vein of male Wistar rats to ablate capsaicin-sensitive C-fibers. When exposed to systemic hypoglycemia (2.76mM) a week later, animals treated with capsaicin demonstrated an 50% to 80% suppression in the sympathoadrenal response when compared to controls.; In Experiment C, animals underwent either 75 min of hypoglycemic exposure or rested on day 1. On day 2, the sympathoadrenal response to systemic hypoglycemia with either peripheral or portal glucose infusion was assessed in both groups of animals. Exposing animals to antecedent hypoglycemia resulted in a 45% to 55% suppression the sympathoadrenal response to systemic hypoglycemia when compared to controls. Furthermore, the 40% suppression in the epinephrine response observed in control animals with portal glucose infusion was eliminated by antecedent hypoglycemia.; From the above experiments we can conclude that: (A) spinal afferents traversing the celiac ganglion, not vagal afferents, are critical for hypoglycemic detection at the portal vein, (B) hypoglycemic detection at the portal vein is mediated by capsaicin-sensitive afferent C-fibers, and (C) a single episode of antecedent hypoglycemia substantially impairs the ability of portal glucose sensors to detect glycemic levels.