To determine the role of apolipoprotein E (apoE) in diabetic hyperlipidemia, we induced diabetes in transgenic mice overexpressing apoE by intravenous injection of streptozotocin (STZ) and examined plasma lipoprotein metabolism in these mice. In STZ-induced diabetic mice, blood glucose levels were > 19 mmol/l (350 mg/dl) and plasma insulin levels were reduced to = 5 pmol/l (1 μU/ml). The diabetic nontransgenic mice developed hypercholesterolemia (plasma total cholesterol level: 4.55 ± 1.32 vs. 1.97 ± 0.13 mmol/l [176 ± 51 vs. 76 ± 5 mg/dl]) and hypertriglyceridemia (plasma triglyceride level: 0.82 ± 0.29 vx. 0.42 ± 0.11 mmol/l [73 ± 26 vs. 37 ± 10 mg/dl]) compared with values before induction of diabetes. In the diabetic nontransgenic mice, enhanced intestinal acylCoA:cholesterol acyltransferase activity was demonstrated, a factor that may contribute to the development of diabetic hyperlipidemia. Induction of apoE remarkably reduced the development of hyperlipidemia in diabetic transgenic mice compared with diabetic nontransgenic mice (plasma cholesterol level: 4.55 ± 1.32 vs. 3.31 ± 0.47 mmol/l [176 ± 51 vs. 128 ± 18 mg/dl], P < 0.01, and plasma triglyceride level: 0.82 ± 0.29 vs. 0.17 ± 0.11 mmol/l [73 ± 26 vs. 15 ± 10 mg/dl], P < 0.01). Plasma lipoprotein analysis by gel filtration chromatography showed that the reduction of plasma cholesterol and triglyceride levels was due to the disappearance of lipoproteins containing apoB. In these studies, we demonstrated the usefulness of STZ-induced diabetes in mice as an animal model for diabetic hyperlipidemia and demonstrated that endogenous induction of apoE in transgenic mice improved diabetic hyperlipidemia.
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Original Articles|
May 01 1995
Overexpression of Apolipoprotein E Prevents Development of Diabetic Hyperlipidemia in Transgenic Mice
Koji Yamamoto;
Koji Yamamoto
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Hongo, Tokyo, Japan
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Hitoshi Shimano;
Hitoshi Shimano
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Hongo, Tokyo, Japan
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Masako Shimada;
Masako Shimada
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Hongo, Tokyo, Japan
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Masako Kawamura;
Masako Kawamura
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Hongo, Tokyo, Japan
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Takanari Gotoda;
Takanari Gotoda
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Hongo, Tokyo, Japan
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Kenji Harada;
Kenji Harada
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Hongo, Tokyo, Japan
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Jun-ichi Ohsuga;
Jun-ichi Ohsuga
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Hongo, Tokyo, Japan
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Yoshi Yazaki;
Yoshi Yazaki
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Hongo, Tokyo, Japan
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Nobuhiro Yamada
Nobuhiro Yamada
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Hongo, Tokyo, Japan
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Address correspondence and reprint requests to Dr. Nobuhiro Yamada, Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Hongo, Tokyo 113, Japan.
Diabetes 1995;44(5):580–585
Article history
Received:
April 11 1994
Revision Received:
January 19 1995
Accepted:
January 19 1995
PubMed:
7729619
Citation
Koji Yamamoto, Hitoshi Shimano, Masako Shimada, Masako Kawamura, Takanari Gotoda, Kenji Harada, Jun-ichi Ohsuga, Yoshi Yazaki, Nobuhiro Yamada; Overexpression of Apolipoprotein E Prevents Development of Diabetic Hyperlipidemia in Transgenic Mice. Diabetes 1 May 1995; 44 (5): 580–585. https://doi.org/10.2337/diab.44.5.580
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