THE ROLE OF LIVER GLUCOSENSORS IN THE INTEGRATED SYMPATHETIC RESPONSE INDUCED BY DEEP HYPOGLYCEMIA IN DOGS

The significance of the portohepatic glucosensors for counterregulation in deep hypoglycemia (i.e., glycemia <2.8 mM) was studied in chronically cannulated male mongrel dogs in the conscious state. A total of 16 experiments were carried out on 6 dogs using the liver clamp technique under hyperinsulinemic conditions (insulin infusion, 39 pmol . min(-1) kg(-1), 0-150 min). The level of glycemia presented to the liver was made to differ from the systemic arterial glucose level via portal glucose infusion. Tracer-determined rates of glucose clearance and hepatic glucose output (HGO) were assessed using D-[3-H-3]glucose (0.26 mu Ci . min(-1)). Three protocols mere used. In protocol I, liver clamp, systemic hypoglycemia at 2.60 +/- 0.09 mM, and liver glycemia at 3.86 +/- 0.05 mM were achieved with portal glucose infusion (28.2 +/- 3.0 mu mol . min(-1) . kg(-1)). For protocol II, glucose was infused peripherally (18.2 +/- 4.3 mu mol . min(-1) . kg(-1)), while systemic and liver glycemia were sustained at deep hypoglycemia, 2.50 +/- 0.08 mM. In protocol III, via peripheral glucose infusion (62.9 +/- 5.8 mu mol . min(-1) . kg(-1)), systemic and liver glycemia were maintained at a level matched to the liver glycemia during protocol I (3.98 +/- 0.05 mM, P > 0.10). When compared with protocols I and III, the catecholamine response above basal was significantly greater during protocol II with liver and systemic deep hypoglycemia (7.30 +/- 1.51 and 2.89 +/- 0.5 nM for epinephrine and norepinephrine, respectively, P < 0.005). These values reflect net increases in the catecholamine responses of 100% and 85% for epinephrine and norepinephrine when compared with protocol I. Glucose clearance was similar among protocols (13.03 +/- 1.26 ml . min(-1) . kg(-1), P > 0.10). HGO was essentially unchanged from basal during protocol II but suppressed during protocols I and III (P < 0.05). These results are consistent with the hypothesis that portohepatic glucosensors play a significant role in eliciting the sympathoadrenal response to deep hypoglycemia.