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-[3-3H]glucose (0.26 microCi.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 mumol.min-1.kg-1). For protocol II, glucose was infused peripherally (18.2 +/- 4.3 mumol.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 mumol.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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, University of Southern California, Los Angeles 90033.
M
M
Hamilton-Wessler
R N
RN
Bergman
J B
JB
Halter
R M
RM
Watanabe
C M
CM
Donovan
D000818:Animals; D001158:Arteries; D001786:Blood Glucose / Q000378:metabolism*; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D006503:Hepatic Veins; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008099:Liver / Q000294:innervation*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine