Hepatocytes from obese zucker rats are resistant to the inhibitory effect of insulin on the secretion of vldl apolipoprotein b and triacylglycerol. Bourgeois, Catherine S., David Wiggins, Reginald Hems, and Geoffrey F. Gibbons. Metabolic Research Laboratory, Nuffield Department of Clinical Medicine, University of Oxford, Radcliffe Infirmary, Woodstock Road, Oxford, OX2 6HE, U.K.
APStracts 2:0076E, 1995.
The effects of insulin (0-780 nM) on the secretion of very-low-density lipoprotein (VLDL) apolipoprotein B (apoB) and triacylglycerol (TAG) in hepatocytes from obese Zucker rats and from their lean litter mates were studied over a total period of 48 h in chemically defined culture medium. Cells from the obese Zucker rats initially secreted more TAG than those from the lean animals. The former cells were resistant to the inhibitory effect of insulin on the secretion of TAG. These changes were accompanied by an increased rate of TAG synthesis. Although the hepatocytes from the obese animals initially secreted less apoB than those from the lean, apoB output from the former cells could not be suppressed by insulin. Prolonging the length of the culture period resulted in the acquisition of sensitivity to the inhibitory effect of insulin in the hepatocytes from the obese rats. This occurred more rapidly for the secretion of TAG than for apoB. Under these conditions, the initial difference in the rate of TAG synthesis in the hepatocytes from the obese and from the lean animals was also abolished.

Received 21 October 1994; accepted in final form 6 April 1995.
APS Manuscript Number E436-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.