Progressive defect in biliary gsh secretion in streptozotocin
-induced diabetic rats.
Lu, Shelly C., John Kuhlenkamp, Huiyuan Wu, Wei-Min Sun, Lee Stone,
Jian Yi, and Neil Kaplowitz.
Division of Gastrointestinal and Liver Diseases, Department of
Medicine, University of Southern California School of Medicine, and
the Department of Veteran Affairs Outpatient Clinic, Los Angeles, CA
90033
APStracts 3:0080G, 1996.
This study examined the effect of streptozotocin-induced diabetes on
biliary GSH efflux. Biliary GSH efflux was measured before and after
acivicin, an irreversible inhibitor of [gamma]-glutamyl
transpeptidase (GGT). One week after streptozotocin treatment, liver
GGT activity doubled in diabetic rats but was inhibited by 90% after
acivicin to comparable levels as controls. Despite maximal GGT
inhibition, biliary GSH efflux in untreated diabetic rats decreased
progressively to 10% of control levels by week 4 and was partially
restored by insulin. The mechanism for the decrease in biliary GSH
efflux was not increased paracellular permeability or decreased
amount of canalicular GSH transporter. GSH transport kinetics, ATP
-stimulated taurocholate and GSSG transport in cLPM prepared from
diabetic and control rats were similar. Inhibition of protein kinase
C with high dose H-7 increased biliary GSH efflux in diabetic animals
to near control basal levels. In conclusion, streptozotocin-induced
diabetic rats exhibit a progressive impairment in biliary GSH
transport. One of the responsible mechanisms is heightened protein
kinase C tone in diabetic animals.
Received 13 November 1995; accepted in final form 30 March 1996.
APS Manuscript Number G485-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 23 April 96