Decreased hepatic glucose production in rats with carbon tetrachloride-induced cirrhosis.
Energy metabolism was studied in fed and fasted rats with carbon tetrachloride (CCl4)-induced cirrhosis. In situ liver perfusion experiments were performed under basal conditions (no substrate added to the perfusate) and after stimulation with glucagon (2 nM) and L-alanine (20 mM). Under basal conditions, oxygen consumption per gram of liver was reduced in cirrhotic rats irrespective of the metabolic state. After addition of glucagon/L-alanine to the perfusate, oxygen consumption increased significantly in fed and fasted control and cirrhotic rats. Under basal conditions, glucose production was reduced by 76% in cirrhotic rats, averaging 0.75 +/- 0.19 vs. 0.18 +/- 0.15 mumol.g liver-1.min-1 in control and cirrhotic livers, respectively (means +/- S.E.M., P < 0.05). After addition of glucagon/L-alanine to the perfusate, glucose production increased in both groups and was reduced by 65% in fed cirrhotic as compared with fed control rats, averaging 3.63 +/- 0.27 vs. 1.27 +/- 0.17 mumol.g liver-1.min-1 in control and cirrhotic rats, respectively (P < 0.05). Stimulated glucose production was linearly correlated with the fractional aminopyrine elimination rate constant (ABT-k), a measure of hepatic function in vivo. After 12 h of fasting, stimulated glucose production was decreased by 15% in control and by 65% in fed cirrhotic rats compared with the fed state, averaging 3.07 +/- 0.22 vs. 0.33 +/- 0.03 mumol.g liver-1.min-1 in control and cirrhotic rats, respectively (P < 0.05). After 24 h of starvation, glucose production was not significantly different between control and cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Krähenbühl
S
S
Department of Clinical Pharmacology, University of Berne, Switzerland.
Reichen
J
J
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism*; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D014508:Urea / Q000378:metabolism
D007773:Lactates; D011773:Pyruvates; D019344:Lactic Acid; D019289:Pyruvic Acid; D014508:Urea; D005934:Glucagon; D005947:Glucose