Compartmental modeling of glucagon kinetics in the conscious dog.
The aim of the present study was to examine glucagon metabolism and distribution using both compartmental-modeling approaches and steady-state organ-balance techniques in conscious, overnight-fasted dogs. Arterial plasma glucose concentrations were clamped at 14 mmol/L with a variable exogenous glucose infusion. Somatostatin was infused to block endogenous secretion of insulin and glucagon. Insulin was replaced intraportally at 2.4 pmol.kg-1.min-1 to maintain basal insulin concentrations in the range from 70 +/- 4 to 95 +/- 12 pmol/L. Glucagon was not given during the control period, but was subsequently infused peripherally in four 1-hour steps of 1.0, 3.0, 6.0, and 3.0 ng.kg-1.min-1. Glucagon levels increased from 0 to 68 +/- 6, 195 +/- 19, 378 +/- 47, and 181 +/- 20 ng/mL. Compartmental analysis of glucagon concentrations showed that glucagon was distributed in one compartment with a volume approximately equal to the plasma volume. The metabolic clearance rate of glucagon was 17.6 mL.kg-1.min-1. The liver cleared 24% of glucagon, and the kidneys, 17%.
Dobbins
R L
RL
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Davis
S N
SN
Neal
D W
DW
Cobelli
C
C
Jaspan
J
J
Cherrington
A D
AD
D000818:Animals; D004285:Dogs; D005260:Female; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D005947:Glucose / Q000096:biosynthesis; D007328:Insulin / Q000097:blood*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation; D008297:Male; D008954:Models, Biological; D009994:Osmolar Concentration; D012079:Renal Circulation
D007328:Insulin; D005934:Glucagon; D005947:Glucose