Effects of Noninsulin-Dependent Diabetes Mellitus on the Uptake of Very Low Density Lipoproteins by Thioglycolate-Elicited Mouse Peritoneal Macrophages*

The lipid-laden foam cells from atherosclerotic lesions appear to be derived from macrophages which have accumulated lipids from plasma lipoproteins. When examined in vitro, thioglycolate-elicited mouse peritoneal macrophages do not accumulate lipids when exposed to normal low density lipoproteins (LDL), but take up very low density lipoproteins (VLDL) or chemically modified LDL with resultant lipid accumulation. Patients with noninsulin-dependent diabetes mellitus (NIDDM) have an increased incidence of atherosclerosis, due in part to disturbances in lipoprotein metabolism. We investigated the possibility that VLDL isolated from patients with NIDDM are taken up by mouse peritoneal macrophages more avidly than normal. Two groups of patients with NIDDM were studied; one group was normotriglyceridemic and the other group was hypertriglyceridemic. The VLDL from both normotriglyceridemic and hypertriglyceridemic patients were enriched in cholesterol and triglyceride compared to that from normal subjects. Thioglycolate-elicited mouse peritoneal macrophages bound and degraded greater amounts of VLDL isolated from patients with NIDDM (both normo- and hypertriglyceridemic) than of VLDL from normal subjects. While normal VLDL caused a marked increase in cellular triglyceride and cholesteryl ester contents in macrophages, VLDL isolated from patients with NIDDM resulted in an even greater cellular accumulation of lipids. These results suggest that the VLDL of patients with NIDDM have alterations in their composition and metabolic behavior. The increased uptake of VLDL by macrophages may contribute to the enhanced atherosclerosis present in NIDDM.