Localization of cholesterol synthesis along villus-crypt axis in diabetic rats

In diabetic animals cholesterol synthesis is increased in the small intestine, and this increase occurs in all segments along the duodenal-ileal axis. In the present study we have determined the sites along the villus-crypt axis in which cholesterol synthesis is increased. In diabetic animals cholesterol synthesis is increased in the proximal small intestine, and this is chiefly due to an increased synthesis in the crypt cells. In the midintestine cholesterol synthesis is increased in all cell fractions, but again the crypt cells are the major site accounting for the increase. In the distal small intestine synthesis is increased in all cell fractions, but the increase is greatest in the upper villus cells. Thus the basis for the increase in intestinal cholesterol synthesis in diabetic animals is dependent on location. Additionally, in the proximal small intestine the increase in synthesis is due to an increased mass of cells, whereas in the distal small intestine the increase is due to an increased synthesis per unit of tissue. In cholesterol-fed diabetic animals we observed a decrease in cholesterol synthesis in the proximal and midintestine that was due to a decrease in synthesis in all cell fractions. This decrease in synthesis is accounted for by a decrease in synthesis per unit of tissue. Restricting food intake in the diabetic animals decreased cholesterol synthesis in all cell layers, and this decrease is due to a decrease in cell mass.(ABSTRACT TRUNCATED AT 250 WORDS)