出版社:American Society for Biochemistry and Molecular Biology
摘要:The factors underlying cardiovascular risk in patients withdiabetes have not been clearly elucidated. Efforts to studythis in mice have been hindered because the usual atherogenicdiets that contain fat and cholesterol also lead to obesityand insulin resistance. We compared plasma glucose, insulin,and atherosclerotic lesion formation in LDL receptor knockout(Ldlr–/–) mice fed diets with varying fat and cholesterolcontent that induced similar lipoprotein profiles. Ldlr–/–mice fed a high-fat diet developed obesity, mild hyperglycemia,hyperinsulinemia, and hypertriglyceridemia. Quantitative andqualitative assessments of atherosclerosis were unchanged indiabetic Ldlr–/– mice fed a high-fat diet comparedwith lean nondiabetic control mice after 20 weeks of diet. Althoughone group of mice fed diets for 40 weeks had larger lesionsat the aortic root, this was associated with a more atherogeniclipoprotein profile. The presence of a human aldose reductasetransgene had no effect on atherosclerosis in fat-fed Ldlr–/–mice with mild diabetes. Our data suggest that when lipoproteinprofiles are similar, addition of fat to a cholesterol-richdiet does not increase atherosclerotic lesion formation in Ldlr–/–mice.Supplementary key words diabetes • insulin resistance • aldose reductase
Abbreviations: ApoE, apolipoprotein E; AR, aldose reductase; FPLC, fast-protein liquid chromatography; HF1, high-fat diet 1; LF1, low-fat diet 1