Streptozotocin-induced increase in cholesterol ester transfer protein (CETP) and its reversal by insulin in transgenic mice expressing human CETP

被引:7
作者
Cheema, SK [1 ]
Rashid-Kolvear, F [1 ]
机构
[1] Mem Univ Newfoundland, Dept Biochem, St Johns, NF A1B 3X9, Canada
关键词
transgenic mice; streptozotocin-induced diabetes; cholesterol ester transfer protein;
D O I
10.1139/Y03-093
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
High plasma triacylglycerol and low high-density lipoprotein levels are risk factors for cardiovascular disease in diabetes. Plasma high-density lipoprotein levels are regulated by cholesterol ester transfer protein (CETP). The regulation of CETP under diabetic conditions is not clear, and this is due to a lack of appropriate models. We used transgenic mice expressing human CETP to study the regulation of this protein under type-1 diabetic conditions and further investigated whether insulin reverses the effect of diabetes. Mice expressing human CETP under the control of its natural flanking region and age-matched littermates not expressing this protein were made diabetic by injecting streptozotocin, and the reversal of diabetes was assessed by injecting insulin. The plasma total cholesterol, low-density lipoprotein-cholesterol, and triacylglycerol concentrations were elevated, whereas high-density lipoprotein-cholesterol concentrations were reduced after the onset of diabetes. Insulin injection partially recovered this effect. The plasma cholesterol ester transfer activity, CETP mass, and hepatic CETP mRNA abundance were significantly higher in diabetic mice that were partially restored by insulin administration. There was a strong correlation between high-density lipoprotein-cholesterol concentrations and cholesterol ester transfer activity. These results suggest that an increase in CETP under diabetic conditions might be a major factor responsible for increased incidence of diabetes-induced atherosclerosis.
引用
收藏
页码:997 / 1004
页数:8
相关论文
共 33 条
[1]  
AGELLON LB, 1991, J BIOL CHEM, V266, P10796
[2]   INTRAPERITONEAL INSULIN THERAPY CORRECTS ABNORMALITIES IN CHOLESTERYL ESTER TRANSFER AND LIPOPROTEIN-LIPASE ACTIVITIES IN INSULIN-DEPENDENT DIABETES-MELLITUS [J].
BAGDADE, JD ;
DUNN, FL ;
ECKEL, RH ;
RITTER, MC .
ARTERIOSCLEROSIS AND THROMBOSIS, 1994, 14 (12) :1933-1939
[3]   ACCELERATED CHOLESTERYL ESTER TRANSFER IN NONINSULIN-DEPENDENT DIABETES-MELLITUS [J].
BAGDADE, JD ;
LANE, JT ;
SUBBAIAH, PV ;
OTTO, ME ;
RITTER, MC .
ATHEROSCLEROSIS, 1993, 104 (1-2) :69-77
[4]   ACCELERATED CHOLESTERYL ESTER TRANSFER IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS [J].
BAGDADE, JD ;
RITTER, MC ;
SUBBAIAH, PV .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1991, 21 (02) :161-167
[5]   Effects of multiple daily insulin injections and intraperitoneal insulin therapy on cholesteryl ester transfer and lipoprotein lipase activities in NIDDM [J].
Bagdade, JD ;
Kelley, DE ;
Henry, RR ;
Eckel, RH ;
Ritter, MC .
DIABETES, 1997, 46 (03) :414-420
[6]  
BAGDADE JD, 1995, J LIPID RES, V36, P759
[7]   MOLECULAR-BASIS OF LIPID TRANSFER PROTEIN-DEFICIENCY IN A FAMILY WITH INCREASED HIGH-DENSITY LIPOPROTEINS [J].
BROWN, ML ;
INAZU, A ;
HESLER, CB ;
AGELLON, LB ;
MANN, C ;
WHITLOCK, ME ;
MARCEL, YL ;
MILNE, RW ;
KOIZUMI, J ;
MABUCHI, H ;
TAKEDA, R ;
TALL, AR .
NATURE, 1989, 342 (6248) :448-451
[8]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[9]   CLONING AND SEQUENCING OF HUMAN CHOLESTERYL ESTER TRANSFER PROTEIN CDNA [J].
DRAYNA, D ;
JARNAGIN, AS ;
MCLEAN, J ;
HENZEL, W ;
KOHR, W ;
FIELDING, C ;
LAWN, R .
NATURE, 1987, 327 (6123) :632-634
[10]  
DULLAART RPF, 1989, DIABETOLOGIA, V32, P14