Importance of Hepatic Glucoreceptors in Sympathoadrenal Response to Hypoglycemia

To ascertain whether hepatic glucoreceptors are important to hypoglycemic counterregulation, a localized euglycemic clamp was employed across the liver during general hypoglycemia. Dogs were infused peripherally with insulin (18–21 pmol · kg⁻¹ · min⁻¹) for 150 min to induce systemic hypoglycemia. During the liver-clamp (LC) protocol, glucose was infused via the portal vein to maintain euglycemia at the liver. In control experiments, i.e., matched infusion (Ml), glucose was infused peripherally at a rate determined to yield similar arterial glycemia levels in the two protocols. Arterial glucose concentrations were not different between protocols during the final hour of insulin infusion (3.26 ± 0.21 and 3.25 ± 0.21 mM during LC and MI, respectively; P = 0.91). Calculated hepatic glucose concentrations during the same period were significantly higher for LC (5.22 ± 0.23 mM) than for MI (3.25 ± 0.21 mM). During MI, both epinephrine and norepinephrine rose significantly from basal values of 562 ± 87 pM and 1.21 ± 0.19 nM to plateaus of 3691 ± 1097 pM (P = 0.0001) and 2.38 ± 0.35 nM (P = 0.0002), respectively. However, during LC, the elevation in epinephrine was suppressed by 42 ± 8% (P = 0.015) relative to MI. Six of seven animals demonstrated a suppression in the norepinephrine response, averaging 32 ± 13% (NS, P = 0.068). The glucagon response to hypoglycemia was unaffected by the level of hepatic glycemia. Hepatic hypoglycemia is essential to produce the full sympathoadrenal response to insulin-induced hypoglycemia.