Celiac-Superior Mesenteric Ganglionectomy, but Not Vagotomy, Suppresses the Sympathoadrenal Response to Insulin-Induced Hypoglycemia

Abstract

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, the 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

Glucose sensing and the pathogenesis of obesity and type 2 diabetes

“…[45][46][47] However, more recent data showed that celiac-superior mesenteric ganglionectomy, but not vagotomy, suppressed the response to insulin-induced hypoglycemia, suggesting that the hepatoportal sensor may indeed participate in triggering glucagon secretion. 48,49 In the central nervous system, sites of glucose detection for the control of counter-regulation are present in the hypothalamus and different brainstem nuclei. In the hypothalamus, lesion studies as well as pharmacological and genetic interferences with glucose detection systems have provided evidence for an important role of the VMH in the control of glucagon secretion.…”

Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony

“…Hepatoportal glucose sensing ( Figure 2) describes a well-characterized phenomenon by which a glucose gradient established between the portal vein and the hepatic artery is sensed, resulting in increased hepatic glucose uptake, increased peripheral glucose disposal, inhibition of counterregulatory hormone secretion, and inhibition of food intake leading to hypo-glycemia (60,61). The actions of this sensor appear to depend on autonomic afferents to the CNS (62,63). However, the precise cellular composition of this sensor and the mechanism by which it senses and communicates remain uncertain.…”

Avenues of Communication between the Brain and Tissues/Organs Involved in Energy Homeostasis

“…Reportedly, a counterregulatory response to moderate systemic hypoglycemia, i.e. sympathetic efferent activation, is attenuated by clamping the liver at euglycemic levels and is disrupted by interruption of sympathetic (but not vagal) afferents from the hepatic portal circulation [58,59]. Collectively, these observations indicate that the afferent autonomic nervous system, including both vagal and sympathetic nerves, from the hepatoportal structure, plays important roles in conveying information regarding peripheral glucose levels to the brain.…”