Afferent innervation of the portal vein has been shown to be critical in hypoglycemic detection, but the neural pathway by which these afferents ascend remains unknown. To ascertain the role of vagal afferents versus spinal afferents in hypoglycemic detection, the catecholamine response to hypoglycemia was assessed in male Wistar rats undergoing hepatic vagotomy (HV), total subdiaphragmatic vagotomy (TSV), or celiac-superior mesenteric ganglionectomy (CSMG). After recovering from the surgery,

more »

... e animals were exposed to a hyperinsulinemic-hypoglycemic clamp, with glucose infused peripherally via the jugular vein. In all animals, systemic hypoglycemia (2.64 ؎ 0.03 mmol/l) was induced via jugular vein insulin infusion (25 mU ⅐ kg ؊1 ⅐ min ؊1 ). No significant differences were observed among the groups with respect to arterial glucose or insulin concentration. When hypoglycemia was induced in shamoperated control animals, epinephrine was observed to rise from a basal value of 0.84 ؎ 0.10 to 25.18 ؎ 1.24 nmol/l. Neither HV nor TSV had any significant impact on the epinephrine response to hypoglycemia. In contrast, CSMG animals demonstrated a significant suppression in the epinephrine response to whole-body hypoglycemia (11.25 ؎ 1.21 vs. 22.32 ؎ 0.86 nmol/l in CSMG vs. controls; P < 0.05). The norepinephrine response for controls, 2.00 ؎ 0.22 at basal and rising to 8.95 ؎ 0.20 nmol/l in hypoglycemia, was not significantly different from that of the HV and TSV animals. As with epinephrine, the norepinephrine response to hypoglycemia was significantly suppressed in CSMG compared with control animals (4.72 ؎ 0.48 vs. 7.15 ؎ 0.76 nmol/l; P < 0.05). These findings are consistent with the idea that hypoglycemic detection at the portal vein is mediated by spinal, and not vagal, glucose-sensitive afferents. Diabetes 54:3258 -3264, 2005 From the