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 (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.
Donovan
C M
CM
University of Southern California, Department of Exercise Science, Los Angeles 90089-0652.
Halter
J B
JB
Bergman
R N
RN
D000311:Adrenal Glands / Q000503:physiopathology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004285:Dogs; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D011956:Receptors, Cell Surface; C027786:glucose receptor; D005934:Glucagon; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine