Glucagon-induced alteration of serum bile acid level in patients with liver cirrhosis.
Percent changes in serum total bile acid level after IV administration of 1 mg glucagon were measured in 61 cirrhotics. Thirty-three of 38 cases with Child's grade A disease showed a reduction of total bile acid level at 15 minutes; this level was maintained in the majority of them until 120 minutes. A similar mode of serial changes in total bile acid level was also shown in the cases with Child's grade B disease. On the other hand, only 2 of 10 cases with Child's grade C showed a reduction of total bile acid level at 15 minutes. Reduction of total bile acid level at 15 minutes after glucagon administration was mimicked by infusion of dibutyryl cyclic adenosine monophosphate. However, in 3 of 6 cases with elevated total bile acid level at 15 minutes after glucagon administration, dibutyryl cyclic adenosine monophosphate induced a reduction of total bile acid level. Also, it was confirmed that glucagon enhances the uptake of taurocholate into freshly isolated rat hepatocytes by activating Na(+)-dependent, carrier-mediated membrane transport system and observed that its effect is associated with elevation of Vmax (0.6114 nmol.min-1 x 10(6) cells-1 without glucagon; 0.975 nmol.min-1 x 10(6) cells-1 in glucagon added) but not with affecting Km (13.58 mumol/L without glucagon; 13.71 mumol/L with glucagon) or protein synthesis which is inhibited by cycloheximide. These observations suggest that glucagon enhances Na(+)-coupled membrane transport of bile acids in the liver and causes the reduction of serum total bile acid level and that a lack of this response may be indicative of membrane dysfunction in the liver.
Tsujii
T
T
Third Department of Internal Medicine, Nara Medical University, Japan.
Morita
T
T
Kubo
R
R
Yamada
M
M
Yamao
J
J
Matsumura
Y
Y
Fujimoto
T
T
Fukui
H
H
Okamoto
Y
Y
D001647:Bile Acids and Salts / Q000097:blood*; D003994:Bucladesine; D000242:Cyclic AMP / Q000097:blood; D005069:Evaluation Studies as Topic; D005260:Female; D005934:Glucagon; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged
D001647:Bile Acids and Salts; D003994:Bucladesine; D005934:Glucagon; D000242:Cyclic AMP