Hyperglucagonism and glucagon resistance in cirrhosis. Paradoxical effect of propranolol on plasma glucagon levels.
Propranolol, a non-selective beta-blocker, is known to decrease glucagon release in normal subjects. The present study was aimed at investigating the effects of propranolol on the hyperglucagonism commonly observed in patients with cirrhosis. Eight cirrhotic patients and 6 matched healthy controls were studied. The plasma concentrations of glucagon, insulin, c-peptide and glucose were measured in basal conditions and after stimulating glucagon secretion by an i.v. infusion of arginine (0.4 g/kg/30 min). The study was repeated 24 h later after inducing beta-blockade by the i.v. infusion of propranolol (10 mg). In baseline conditions, patients with cirrhosis, despite normal levels of insulin and glucose, had a marked hyperglucagonism (654 +/- 303 pg/ml vs. 269 +/- 90 in controls, P less than 0.01). Prior to propranolol, arginine infusion caused greater glucagon release in cirrhotics (71 +/- 31 ng.h.ml-1) than in controls (33 +/- 17 ng.h.ml-1, P less than 0.02), but despite a similar insulin secretion (assessed from c-peptide), blood glucose did not increase. After propranolol, glucagon secretion decreased as expected in controls (29 +/- 12 ng.h.ml-1, P less than 0.05) but experienced a paradoxical increase in cirrhotics (113 +/- 64 ng.h.ml-1, P less than 0.05). Again, despite the marked increase in glucagon release, there was no increase in glucose production, providing further evidence of the glucagon resistance that accompanies hyperglucagonism in cirrhosis. Our results suggest that hyperglucagonism with glucagon resistance might be the initial disturbance in carbohydrate metabolism in patients with cirrhosis. Contrary to what could be expected, propranolol does not correct but further accentuates this disturbance.
Silva
G
G
Liver Unit, Hospital Clinic i Provincial, University of Barcelona, School of Medicine, Spain.
Gomis
R
R
Bosch
J
J
Casamitjana
R
R
Mastai
R
R
Navasa
M
M
Rivera
F
F
Rodés
J
J
D000328:Adult; D001120:Arginine; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D004351:Drug Resistance; D005260:Female; D005934:Glucagon / Q000097:blood*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000503:physiopathology*; D008104:Liver Cirrhosis, Alcoholic / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011433:Propranolol
D001786:Blood Glucose; D002096:C-Peptide; D005934:Glucagon; D001120:Arginine; D011433:Propranolol