Streptozotocin-induced diabetes in human apolipoprotein B transgenic mice:effects on lipoproteins and atherosclerosis

The effects of diabetes and lipoprotein lipase (LpL) on plasma lipids were studied in mice expressing human apolipoprotein B (HuBTg). Our overall obje ctive was to produce a diabetic mouse model in which the sole effects of bl ood glucose elevation on atherosclerosis could be assessed, Mice were made diabetic by intraperitoneal injection of streptozotocin, which led to a 2- to 2.5-fold increase in plasma glucose, Lipids were assessed in mice on cho w and on an atherogenic Western type, diet (WTD), consisting of 21% (wt/wt) fat and 0.15% (wt/wt) cholesterol, Plasma triglyceride and cholesterol wer e the same in diabetic and non diabetic mice on the chow diet, On the WTD, male diabetic HuBTg mice had a >50% increase in plasma cholesterol and more very low density lipoprotein (VLDL) cholesterol and triglyceride as assess ed by FPLC analysis. A Triton study showed no increase in triglyceride or a polipoprotein B production, suggesting that the accumulation of VLDL was du e to a decrease in lipoprotein clearance, Surprisingly, the VLDL increase i n these mice was not due to a decrease in LpL activity in postheparin plasm a. To test whether LpL overexpression would alter these diabetes-induced li poprotein changes, HuBTg mice were crossed with mice expressing human LpL i n muscle, LpL overexpression reduced plasma triglyceride, but not cholester ol, in male mice on WTD, Aortic root atherosclerosis assessed in 32-week-ol d mice on the WTD was not greater in diabetic mice. In summary, diabetes pr imarily increased plasma VLDL in HuBTg mice. LpL activity was not decreased in these animals, However, additional LpL expression eliminated the diabet ic lipoprotein changes, These mice did not have more atherosclerosis with d iabetes.