| Traditionally ascribed to the central nervous system, glucosensors involved in sympathoadrenal counterregulation against hypoglycemia have now been constrained to the portohepatic region. The purpose of the current investigations was to further localize glucosensors to either the liver or hepatic vasculature, and ascertain neural mediation of this sensing mechanism. Animals were cannulated in the portal vein either adjacent to (POR-ADJ) or distal from (POR-DIST) the liver. Animals participated in one of three hyperinsulinemic-hypoglycemic clamp protocols distinguished by the site of glucose infusion. Whole body hypoglycemia was induced with either liver and portal vein glucose normalization (POR-DIST), or liver glucose normalization alone (POR-ADJ). Despite cerebral hypoglycemia, a significant suppression in the sympathoadrenal response was observed during liver and portal vein glucose normalization. In contrast, liver glucose normalization alone, resulted in a full sympathoadrenal response, not significantly different from whole body hypoglycemia. These findings are consistent with localization of glucosensors to the portal vein, not the liver.;As a portal glucosensor locus attaches significance to pre-hepatic glycemia, we sought to determine the presence of glucosensors in the hepatic artery. Animals were cannulated in the hepatic artery allowing for hepatic artery and liver glucose normalization during systemic hypoglycemia. Unlike the previous findings for the portal vein, normalization of hepatic artery glycemia had no impact on the sympathoadrenal response to systemic hypoglycemia. These findings indicate an apparent lack of glucosensors in the hepatic artery, and confirm findings regarding a lack of glucose sensing by the liver.;The importance of portal vein afferents in hypoglycemic detection and sympathoadrenal counterregulation was assessed following phenol induced portal denervation. The catecholamine response to whole body hypoglycemia was significantly blunted in portally denervated animals (PDN). In contrast to findings in SHAM operated animals, in PDN, portal glucose normalization had no impact on the sympathoadrenal response to systemic hypoglycemia when compared to whole body hypoglycemia. That is, no suppression in the sympathoadrenal response to systemic hypoglycemia was observed during portal vein glucose normalization for PDN. Results indicate that portal vein afferents are critical for hypoglycemic detection and normal sympathoadrenal counterregulation. |
