Failure of glucagon to stimulate hepatic glycogenolysis in well-nourished patients with mild cirrhosis.
The ability of glucagon to stimulate hepatic glucose production (HGP) was studied in clinically stable cirrhotic patients (n = 8) who had, based on long-term follow-up evaluation, relatively good liver function (Child-Pugh A) and whose dietary intake and physical characteristics were comparable to those of healthy control subjects (n = 8). Plasma glucagon concentration was slightly but not significantly increased in cirrhotic patients versus control subjects in the basal state (190 +/- 41 v 126 +/- 24 pg/mL, P = NS) and during a continuous 180-minute glucagon infusion at 3 ng/kg/min (349 +/- 56 v 243 +/- 37, P = NS). The increment in plasma glucagon level (+164 +/- 57 v +127 +/- 35, P = NS) also was slightly greater in the cirrhotic group. HGP (measured with [6-3H]-glucose) in the basal state was similar in cirrhotic and control subjects (1.79 +/- 0.09 v 1.94 +/- 0.15 mg/kg/min, P = NS). In cirrhotic patients, stimulation of HGP by glucagon was blunted during the first 15 to 30 minutes of the infusion period (representing glucagon's predominant effect on glycogenolysis; 0.23 +/- 0.20 v 1.06 +/- 0.19 mg/kg/min, P < .05), but it was not different from that in control subjects during the remaining course of the experiment (30 to 180 minutes). Basal plasma insulin and C-peptide concentrations did not change from baseline during the glucagon infusion in cirrhotics, whereas they increased slightly but not significantly in controls. These data demonstrate that even in the early stages of cirrhosis, the liver is resistant to the stimulatory effect of glucagon on hepatic glycogenolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Petrides
A S
AS
Department of Medicine, Heinrich-Heine University, Düsseldorf, Germany.
De Fronzo
R A
RA
D000328:Adult; D000596:Amino Acids / Q000032:analysis / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D006003:Glycogen / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D013997:Time Factors
D000596:Amino Acids; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D006003:Glycogen; D005934:Glucagon; D005947:Glucose