The role of liver glucosensors in the integrated sympathetic response induced by deep hypoglycemia in dogs

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Abstract
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-[3-3H]glucose (0.26 μCi · min−1). Three protocols were 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 μmol · min−1 · kg−1). For protocol II, glucose was infused peripherally (18.2 ± 4.3 μmol · 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 μmol · 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.