title: Stimulation of cholesterol and lipid synthesis by insulin in familial hypercholesterolemic fibroblasts.
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.
mesh_terms: D000085:Acetates / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis*; D005227:Fatty Acids / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008055:Lipids / Q000096:biosynthesis*; D010743:Phospholipids / Q000096:biosynthesis
chemical_list: D000085:Acetates; D005227:Fatty Acids; D007328:Insulin; D008055:Lipids; D010743:Phospholipids; D002784:Cholesterol