CHYLOMICRON AND CHYLOMICRON REMNANT METABOLISM IN STZ-INDUCED DIABETIC RATS

The small intestine is an important source of plasma lipoproteins in various diabetic animal models. This increase in intestinally derived lipids originate from diet and/or primary lipid synthesis, and these lipids are transported to the plasma as chylomicrons (CM). The understanding of the metabolism of these triglyceride-rich particles has assumed considerable importance. When [C-14]cholesterol and [H-3]triglyceride-labeled normal CM were injected into rats, we found no difference in either the initial plasma clearance or in the hepatic uptake between control and diabetic rats. However, the clearance rate and hepatic uptake were dependent on the triglyceride concentration administered. Both the initial clearance and hepatic uptake in control and diabetic rats slowed to a similar extent with increasing triglyceride dose demonstrating the influence of the size of the endogenous triglyceride pool on the metabolic rate of CM. No difference was found in the clearance of CM remnants between control and diabetic rats when examined both in vivo and in liver perfusion experiments. Furthermore, with affinitY chromatography, we found that the increase in serum triglycerides levels in diabetic rats was due to triglyceride-rich very-low-density lipoproteins and/or CM and not to the accumulation of remnants, which supports the observation that remnant clearance is not IMPaired. Despite the absence of alterations in bulk CM metabolism, we observed an increase in CM-CM remnant binding to the endothelium in hearts of diabetic rats. Both the increased delivery to the liver and the increased binding of CM-CM remnants to endothelial surfaces could contribute to the increased risk of atherosclerosis in diabetes.