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Effect of Cholesterol-Feeding on Tissue Glucose Uptake, Insulin-Degradation, Serum Lipids and Serum Lipoperoxide Levels in Rabbits¹

The University of Michigan, M5170 Human Nutrition Program, School of Public Health, Ann Arbor, Michigan 48109

The experiment was conducted to study the effect of cholesterol-feeding on tissue glucose uptake, serum insulin concentration and other metabolic parameters in rabbits. Rabbits were fed a stock diet with 2% vegetable oil or this basal diet enriched with 0.5% cholesterol for a period of 48 days. Cholesterol-feeding markedly increased total serum cholesterol, but decreased serum high density lipoprotein (HDL) cholesterol levels. Cholesterol-feeding also increased serum unesterified fatty acid and lipid peroxide concentrations. The concentration of serum insulin in cholesterol-fed rabbits was not significantly changed. Cholesterol-fed rabbits showed increased 3-0-[methyl-¹⁴C]D-glucose uptake in the diaphragm and the aorta incubated in the presence of insulin in vitro. Hepatic glutathione-insulin transhydrogenase activity in the microsomal fraction was not changed by cholesterol-feeding when the microsomal preparations were not pre-treated with Triton X-100, but was significantly elevated when pretreated with Triton X-100. Liver glucose-ß-phosphate dehydrogenase and NADP-malate dehydrogenase activities were lower in rabbits fed the cholesterol-supplemented diet. Results of this study indicate that cholesterol-feeding can increase vascular permeability to glucose, decrease serum HDL-cholesterol, and increase serum unesterified fatty acid and lipoperoxide levels. These metabolic alterations may play an important role in the pathogenesis of atherosclerosis.

KEY WORDS: • cholesterol • HDL-cholesterol • glutathione-insulin transhydrogenase • glucose-6-phosphate dehydrogenase • NADP-malate dehydrogenase • lipoperoxide • unesterified fatty acid • insulin • glucose uptake

¹ The work was supported in part by a grant-in-aid from the Michigan Heart Association.

Manuscript received 4 August 1978.