Cholesterol synthesis is increased two- to threefold in the small intestine of diabetic rats. We have observed, in three separate experiments, that the characteristic increase in small intestinal cholesterol synthesis (SICS) in diabetic rats was prevented by total gastrectomy. Food intake was increased twofold, and the small intestine hypertrophied in the gastrectomized diabetic animals. In normal animals, total gastrectomy resulted in only a very small increase in intestinal cholesterol synthesis. In hyperphagic lactating animals, total gastrectomy did not prevent the characteristic increase in SICS that is usually observed in this hyperphagic model. These results indicatethat the effects of total gastrectomy on preventing an increase in SICS are relatively specific for the diabetic state. The mechanism by which total gastrectomy prevents the increase in intestinalcholesterol synthesis in diabetic animals is unknown. Vagotomy did not prevent the typical increase in intestinal synthesis in diabetic animals. Additionally, selectively removing either the antrum or fundus of the stomach did not prevent the increase in SICS in diabetic animals, indicating that the inhibition requires the removal of the entire stomach. It can be speculated that the stomach produces a substance that induces the increase in SICS observed in diabetic animals and that total gastrectomy removes this stimulatory substance.

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