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Journal of Lipid Research, Vol 27, 915-924, Copyright © 1986 by Lipid Research, Inc.
T Akiyoshi, K Uchida, H Takase, Y Nomura and N Takeuchi
Normal and alloxan-diabetic male mice (Crj-ICR) were fed a diet containing
0.5% cholesterol for 5 and 10 weeks, and gallbladder bile was analyzed for
cholesterol, phospholipids and bile acids, feces for sterols and bile
acids, and plasma and liver for cholesterol, phospholipids, and
triglycerides. Normal mice developed no gallstones but the diabetic mice
developed cholesterol gallstones with an incidence of 70% by 5 weeks and
80% by 10 weeks after feeding of the cholesterol diet. Diabetic mice fed
the ordinary diet also developed stones (23%) by 10 weeks. In the diabetic
mice, the gallbladder was enlarged about threefold, and biliary lipid
concentration, diet intake, and fecal excretion of sterols and bile acids
increased but body weight decreased. Cholic acid and beta-muricholic acid
comprised over 40% each of the total biliary bile acids in normal mice, but
cholic acid increased to about 80% and beta-muricholic acid decreased to a
few percent in the diabetic mice. Fecal excretion of bile acids increased
after cholesterol feeding in both normal and diabetic mice, but the
increased bile acid in the normal animals was beta-muricholic acid and that
in the diabetic mice was deoxycholic acid. The mice that developed
gallstones showed a marked increase in biliary cholesterol value and
decreases in gallbladder bile and bile acid concentration, but no
difference in biliary and fecal bile acid composition, bile acid synthesis,
fecal sterols, or plasma and liver lipid levels. Cholesterol absorption was
increased in the diabetic mice when examined by plasma 14C/3H ratio and
fecal 14C-labeled sterol excretion after a single oral administration of
[14C]cholesterol and a simultaneous intravenous injection of
[3H]cholesterol. These data led to the conclusion that cholesterol
gallstones developed in alloxan-diabetic mice fed excess cholesterol, due
to the hyperphagia and the enhancement of cholesterol absorption caused by
increases in the synthesis and secretion of cholic acid.
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Cholesterol gallstones in alloxan-diabetic mice
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