Abstract

A series of experiments was conducted to elucidate the mechanism by which cholesterol feeding decreases serum insulin levels in rats and to determine the effect of this reduced insulin level on glucose metabolism. Rats were fed a casein-sucrose-soybean oil basal diet or this basal diet supplemented with 1% cholesterol (dissolved in hot oil) for periods longer than 30 days. Cholesterol feeding resulted in a decrease in serum insulin concentrations, although the decrease was not always significant. Cholesterol feeding did not affect fasting blood glucose levels, glucose tolerance, glucose-induced insulin release, pancreatic insulin content, in vivo insulin sensitivity, or in vitro glucose utilization in diaphragm and adipose tissue, but it significantly elevated the activity of liver glutathione-insulin transhydrogenase. On a per liver basis, the activity of this enzyme was approximately doubled. Results of this study suggest that cholesterol feeding has no significant effect on glucose utilization, but it can lead to a decrease in serum insulin concentration, probably by increasing the rate of insulin degradation in the liver.

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