Effects of streptozotocin-induced diabetes in apolipoprotein AI deficient mice


      During the past decade a number of investigators have attempted to develop mouse models of diabetic macrovascular disease. Hyperglycemia might increase vascular damage because it increases oxidant stress. For this reason we studied animals that were deficient in HDL; HDL is widely believed to protect against oxidant stress. An inbred line of mice doubly deficient in LDL receptor and apoAI was made diabetic with streptozotocin (STZ); control mice had an average glucose of 7.2±2 mmol/l and STZ-treated mice had an average glucose of 19.4±6.5 mmol/l. The animals were fed a high cholesterol but low fat diet leading to plasma cholesterol levels of 9.4±1.6 mmol/l in control animals and 10.1±1.8 mmol/l in STZ-treated mice. The control and STZ-treated animals had similar plasma lipoprotein profiles. Atherosclerosis assessed at 23 weeks averaged 38154 μm2 in control and 32962 μm2 in STZ-treated mice. Therefore STZ-induced diabetes does not alter plasma lipoproteins or atherosclerosis in HDL deficient mice.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Park L.
        • Raman K.G.
        • Lee K.J.
        • Lu Y.
        • Ferran Jr., L.J.
        • Chow W.S.
        • et al.
        Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts.
        Nat. Med. 1998; 4: 1025-1031
        • Kako Y.
        • Masse M.
        • Huang L.S.
        • Tall A.R.
        • Goldberg I.J.
        Lipoprotein lipase deficiency and CETP in streptozotocin-treated apoB-expressing mice.
        J. Lipid Res. 2002; 43: 872-877
        • Maclean P.S.
        • Joseph B.F.
        • Vadlamudi S.
        • Bradfield J.F.
        • Burden H.W.
        • Barakat H.A.
        Expression of human cholesteryl ester transfer protein eliminates the formation of diet-induced atherosclerotic lesions in the proximal aorta of Db/Db mice.
        Circulation. 2000; 102: II-231
        • Hasty A.H.
        • Shimano H.
        • Osuga J.
        • Namatame I.
        • Takahashi A.
        • Yahagi N.
        • et al.
        Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice lacking both leptin and the low density lipoprotein receptor.
        J. Biol. Chem. 2001; 276: 37402-37408
        • Reaven P.
        • Merat S.
        • Casanada F.
        • Sutphin M.
        • Palinski W.
        Effect of streptozotocin-induced hyperglycemia on lipid profiles formation of advanced glycation endproducts in lesions, and extent of atherosclerosis in LDL receptor-deficient mice.
        Arterioscler. Thromb. Vasc. Biol. 1997; 17: 2250-2256
        • Kako Y.
        • Huang L.S.
        • Yang J.
        • Katopodis T.
        • Ramakrishnan R.
        • Goldberg I.J.
        Streptozotocin-induced diabetes in human apolipoprotein B transgenic mice. Effects On lipoproteins and atherosclerosis.
        J. Lipid Res. 1999; 40: 2185-2194
        • Collins A.R.
        • Meehan W.P.
        • Kintscher U.
        • Jackson S.
        • Wakino S.
        • Noh G.
        • et al.
        Troglitazone inhibits formation of early atherosclerotic lesions in diabetic and nondiabetic low density lipoprotein receptor-deficient mice.
        Arterioscler. Thromb. Vasc. Biol. 2001; 21: 365-371
        • Li A.C.
        • Brown K.K.
        • Silvestre M.J.
        • Willson T.M.
        • Palinski W.
        • Glass C.K.
        Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice.
        J. Clin. Invest. 2000; 106: 523-531
        • Keren P.
        • George J.
        • Shaish A.
        • Levkovitz H.
        • Janakovic Z.
        • Afek A.
        • et al.
        Effect of hyperglycemia and hyperlipidemia on atherosclerosis in LDL receptor-deficient mice: establishment of a combined model and association with heat shock protein 65 immunity.
        Diabetes. 2000; 49: 1064-1069
        • Brownlee M.
        Advanced protein glycosylation in diabetes and aging.
        Annu. Rev. Med. 1995; 46: 223-234
        • Ginsberg H.N.
        Insulin resistance and cardiovascular disease.
        J. Clin. Invest. 2000; 106: 453-458
        • Semenkovich C.F.
        • Heinecke J.W.
        The mystery of diabetes and atherosclerosis: time for a new plot.
        Diabetes. 1997; 46: 327-334
        • Van Lenten B.J.
        • Navab M.
        • Shih D.
        • Fogelman A.M.
        • Lusis A.J.
        The role of high-density lipoproteins in oxidation and inflammation.
        Trends Cardiovasc. Med. 2001; 11: 155-161
        • Ishibashi S.
        • Brown M.S.
        • Goldstein J.L.
        • Gerard R.D.
        • Hammer R.E.
        • Herz J.
        Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery.
        J. Clin. Invest. 1993; 92: 883-893
        • Plump A.S.
        • Erickson S.K.
        • Weng W.
        • Partin J.S.
        • Breslow J.L.
        • Williams D.L.
        Apolipoprotein A-I is required for cholesteryl ester accumulation in steroidogenic cells and for normal adrenal steroid production.
        J. Clin. Invest. 1996; 97: 2660-2671
        • Voyiaziakis E.
        • Goldberg I.J.
        • Plump A.S.
        • Rubin E.M.
        • Breslow J.L.
        • Huang L.S.
        ApoA-I deficiency causes both hypertriglyceridemia and increased atherosclerosis in human apoB transgenic mice.
        J. Lipid Res. 1998; 39: 313-321
        • Lusis A.J.
        • Taylor B.A.
        • Wangenstein R.W.
        • LeBoeuf R.C.
        Genetic control of lipid transport in mice II genes controlling structure of high density lipoproteins.
        J. Biol. Chem. 1983; 258: 5071-5078
        • Frank S.L.
        • Taylor B.A.
        • Lusis A.J.
        Linkage of the mouse LDL receptor gene on chromosome 9.
        Genomics. 1989; 5: 646-648
        • Kunjathoor V.V.
        • Wilson D.L.
        • LeBoeuf R.C.
        Increased atherosclerosis in streptozotocin-induced diabetic mice.
        J. Clin. Invest. 1996; 97: 1767-1773
        • Nordestgaard B.G.
        • Stender S.
        • Kjeldsen K.
        Reduced atherogenesis in cholesterol-fed diabetic rabbits giant lipoproteins do not enter the arterial wall.
        Arteriosclerosis. 1988; 8: 421-428
        • Dixon J.L.
        • Stoops J.D.
        • Parker J.L.
        • Laughlin M.H.
        • Weisman G.A.
        • Sturek M.
        Dyslipidemia and vascular dysfunction in diabetic pigs fed an atherogenic diet.
        Arterioscler. Thromb. Vasc. Biol. 1999; 19: 2981-2992
        • Merat S.
        • Casanada F.
        • Sutphin M.
        • Palinski W.
        • Reaven P.D.
        Western-type diets induce insulin resistance and hyperinsulinemia in LDL receptor-deficient mice but do not increase aortic atherosclerosis compared with normoinsulinemic mice in which similar plasma cholesterol levels are achieved by a fructose-rich diet.
        Arterioscler. Thromb. Vasc. Biol. 1999; 19: 1223-1230
        • Schreyer S.A.
        • Wilson D.L.
        • LeBoeuf R.C.
        C57BL/6 mice fed high fat diets as models for diabetes-accelerated atherosclerosis.
        Atherosclerosis. 1998; 136: 17-24
        • Miwa K.
        • Nakagawa K.
        Risk factors that discriminate ‘high-risk’ from ‘low-risk’ Japanese patients with coronary artery disease.
        Jpn. Circ. J. 2000; 64: 825-830
        • Yamasaki Y.
        • Kodama M.
        • Nishizawa H.
        • Sakamoto K.
        • Matsuhisa M.
        • Kajimoto Y.
        • et al.
        Carotid intima-media thickness in Japanese type 2 diabetic subjects: predictors of progression and relationship with incident coronary heart disease.
        Diabetes Care. 2000; 23: 1310-1315