Stimulation of cholesterol and lipid synthesis by insulin in familial hypercholesterolemic fibroblasts |
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Authors: | L F Amorosa A K Khachadurian M A Islam T T Yamin |
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Affiliation: | 1. Edward J. Bloustein School of Planning and Public Policy, Rutgers University, New Brunswick, NJ, USA;4. Lafayette College, Easton, PA, USA;5. U.S. Fund for UNICEF, New York, NY, USA |
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Abstract: | Cultured skin fibroblasts from two patients with homozygous familial hypercholesterolemia and three normal subjects were preincubated for 24 hours in medium containing 10% delipidated serum with insulin concentrations of 0.4, 4, or 40 ng/mL. [14C]acetate incorporation into total lipids, cholesterol, and phospholipids was significantly increased in familial hypercholesterolemic cells at insulin concentrations of 0.4 and 4 ng/mL, which had no effect in normal cells. When the data were normalized as percent stimulation over control for individual experiments, [14C]acetate incorporation into cholesterol was comparable at 40 ng/mL in both cell types. Similar results were obtained in cells preincubated in serum free artificial medium. Coordinate increases in the activity of 3-hydroxy-3-methylglutaryl CoA reductase in response to insulin were not found. These studies show that familial hypercholesterolemic cells have an altered lipogenic response to low concentrations of insulin. |
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