Elucidation of the origin and contribution of hepatoportal and central nervous system glucose sensors mediating hypoglycemic detection.

摘要

Hypoglycemic detection has been historically attributed to activity of specialized neurons within the central nervous system (CNS). More recently, the primacy of CNS glucose sensors has been challenged as afferents ascending from the hepatic portal vein have been shown to be critical for engendering a full sympathoadrenal response during systemic hypoglycemia. While the contribution of hepatoportal glucose sensors has been repeatedly verified, the aims of the present dissertation were (1) to determine whether the adjoining feed vessel (superior mesenteric vein) contain additional critical glucose sensors augmenting hypoglycemic detection at the portal vein, (2) to ascertain the relative contribution of hepatoportal glucose sensors vs. those of the CNS towards hypoglycemic detection under conditions of varying rates of glycemic decline and lastly (3) to examine the role of central glycemia in the sympathoadrenal response to systemic hypoglycemia, under conditions previously shown to be mediated primarily by hepatic portal vein glucose sensors.;Three separate experiments were conducted to address the aforementioned subject matters. For the first two experiments, male Wistar rats underwent selective denervation of hepatic portal and/or superior mesenteric veins and were subsequently exposed to either a slowly or rapidly developing insulin-induced hypoglycemia. Results suggest that glucose sensors in the superior mesenteric vein, along with those of the portal vein, constitute an important locus for hypoglycemic detection mediating over 90% of the sympathoadrenal response. Additionally, while the magnitude of the sympathoadrenal response is unaffected by the rate of fall in glycemia, the locus for glycemic detection shifts away from the portal-mesenteric region as the rate of fall increases.;To establish whether central glycemia modulates peripheral hypoglycemic detection, male Wistar rats underwent selective unilateral cannulation of carotid artery and jugular vein in conjunction to or without bilateral occlusion of vertebral arteries. Normalization of brain glycemia suppressed the sympathoadrenal response to systemic hypoglycemia, attenuating hypoglycemic inputs from the portal-mesenteric glucose sensors. For the epinephrine response, hindbrain glycemia appeared primary, while integration of the norepinephrine response was more widely distributed in the brain.