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 (MI),
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.