The disappearance from the circulation of chylomicrons obtained from control and diabetic rats.

Abstract

Previous studies have demonstrated that cholesterol synthesis is increased in the small intestine of diabetic animals and that there is an increased transport of this newly synthesized cholesterol from the small intestine into the circulation. Chylomicrons play an important role in the transport of cholesterol from the small intestine into the circulation, and the present study compared the rates of disappearance from the circulation and the fate of chylomicron cholesterol obtained from control and diabetic animals when administered to either intact control or diabetic rats. Thoracic duct lymph was collected from normal and diabetic rats after the administration of [14C]cholesterol and [3H]vitamin A1. The labeled chylomicrons were isolated by centrifugation and then administered to either control or diabetic rats. The major observation of this study is that chylomicron-associated sterols obtained from diabetic animals were cleared from the circulation in a normal manner. If one compares the rate of disappearance of either [3H]vitamin A1 or [14C] cholesterol-labeled normal chylomicrons administered to control animals with that of labeled diabetic chylomicrons administered to diabetic animals, the half-times in the circulation are almost identical (control: [3H]vitamin A1 t 1/2, 3.6 min; [14C]cholesterol t 1/2, 5.7 min; diabetic: [3H]vitamin A1 t 1/2, 3.5 min; [14C]cholesterol t 1/2, 4.4 min). In both experimental situations the rapid disappearance of [14C]cholesterol was associated with the appearance of [14C]cholesterol in the liver. Very little [14C]cholesterol was present in tissues other than liver, indicating that the rapid removal of labeled chylomicron remnants from the circulation was accounted for by hepatic uptake. These results demonstrate that in diabetic animals chylomicron-associated sterols are cleared from the circulation normally and that the bulk of intestinally derived cholesterol carried in the chylomicron lipoprotein fraction is rapidly delivered to the liver, where it could potentially influence lipoprotein metabolism.