Glucagon enhances bile flow, bilirubin uridine diphosphate-glucuronyltransferase activity and biliary bilirubin monoconjugate excretion in the rat.
Intravenous infusion of glucagon (100 micrograms/hr/100 g body weight) in rats produces a 20 to 35% increase in bile flow and enhances the activity of hepatic bilirubin uridine diphosphate-glucuronyltransferase to 132% after a 90 min infusion. When a bilirubin load is given to produce a constant and apparently maximal biliary bilirubin excretion rate (or transport maximum) the administration of glucagon increased the bilirubin transport maximum. The excretion rate of bilirubin monoglucuronides was more enhanced than that of diglucuronide. The enhanced rate of glucuronidation, assayed in vitro, correlated with the augmented biliary output and inversely with the plasma unconjugated bilirubin levels. It is concluded that glucagon, at the dosage used, leads to a higher formation rate of bilirubin monoconjugates and that the choleresis, also induced by the hormone, enhances the biliary secretion of the monoconjugates formed. The enhanced conjugation results in a decreased plasma concentration of unconjugated bile pigment and the associated choleresis leads to a decreased di- to monoconjugate ratio, opposite to what has been observed during bilirubinostasis and cholestasis. The secretory efficacy, as assessed from the bile-to-plasma concentration ratio, is enhanced for all bilirubin pigments after glucagon administration.
Ricci
G L
GL
Department of Medical Research, Catholic University of Leuven, Belgium.
Michiels
R
R
De Groote
J
J
Fevery
J
J
D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D001663:Bilirubin / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology*; D005964:Glucosyltransferases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D005934:Glucagon; D005964:Glucosyltransferases; C035814:bilirubin UDP-glucosyltransferase; D001663:Bilirubin