Yamane M, Jiao S, Kihara S, Shimomura I, Yanagi K, Tokunaga K, Kawata S, Odaka H, Ikeda H, Yamashita S
Second Department of Internal Medicine, Osaka University Medical School, Japan.
J Lipid Res. 1995 Aug;36(8):1676-85.
To assess the alteration of apolipoprotein (apo) B mRNA editing in non-insulin-dependent diabetes mellitus (NIDDM), we measured plasma apoB-100 and apoB-48 levels and apoB mRNA editing efficiency in the liver and intestine from GK (Goto-Kakizaki) rats, a genetically NIDDM animal. Male GK rats and control littermates, aged 25 weeks, were used in this study. Ventromedial hypothalamus (VMH)-lesioned control rats were used as hyperinsulinemic models. VMH-lesioned GK rats (GK+VMH) were treated as an insulin-exhausted NIDDM model. Plasma cholesterol and triglyceride levels were increased in GK rats. Very low density lipoprotein (VLDL)-triglyceride and low density lipoprotein (LDL)-cholesterol concentrations were significantly higher in GK rats than in controls. The increase of VLDL-triglyceride was most marked in GK+VMH rats. Plasma apoB-48 levels, quantified by immunoblot, were increased in GK rats. However, apoB-100 levels were minimally elevated in GK rats. Therefore, the apoB-48/apoB-100 ratio was remarkably increased in GK rats. ApoB mRNA editing was analyzed by reverse transcriptase-polymerase chain reaction coupled with dideoxynucleotide chain termination assay. The ratio of apoB-48-type cDNA to apoB-100-type cDNA was significantly increased in the liver from GK rats compared with controls. Although the development of the VMH lesion increased plasma apoB-48 levels, it had no effect on the proportion of apoB-48-type to apoB-100-type cDNA in the liver from both GK and control littermates. ApoB mRNA in the intestine was almost totally edited (approximately 95%). Intestinal apoB-48/apoB-100 cDNA ratio showed no significant difference among the four groups. In conclusion, an enhanced apoB mRNA editing was indicated in the non-insulin-dependent diabetic rats, which might contribute to the increase of plasma apoB-48 levels.
为评估非胰岛素依赖型糖尿病（NIDDM）中载脂蛋白（apo）B mRNA编辑的改变，我们检测了遗传性NIDDM动物GK（Goto-Kakizaki）大鼠肝脏和肠道中的血浆apoB-100和apoB-48水平以及apoB mRNA编辑效率。本研究使用了25周龄的雄性GK大鼠及其对照同窝仔鼠。腹内侧下丘脑（VMH）损伤的对照大鼠用作高胰岛素血症模型。VMH损伤的GK大鼠（GK+VMH）作为胰岛素耗竭的NIDDM模型。GK大鼠的血浆胆固醇和甘油三酯水平升高。GK大鼠的极低密度脂蛋白（VLDL）-甘油三酯和低密度脂蛋白（LDL）-胆固醇浓度显著高于对照组。GK+VMH大鼠中VLDL-甘油三酯的升高最为明显。通过免疫印迹定量的血浆apoB-48水平在GK大鼠中升高。然而，GK大鼠中apoB-100水平仅略有升高。因此，GK大鼠中apoB-48/apoB-100比值显著增加。通过逆转录聚合酶链反应结合双脱氧核苷酸链终止法分析apoB mRNA编辑。与对照组相比，GK大鼠肝脏中apoB-48型cDNA与apoB-100型cDNA的比值显著增加。尽管VMH损伤的发展增加了血浆apoB-48水平，但对GK大鼠和对照同窝仔鼠肝脏中apoB-48型与apoB-100型cDNA的比例均无影响。肠道中的apoB mRNA几乎完全被编辑（约95%）。四组之间肠道apoB-48/apoB-100 cDNA比值无显著差异。总之，非胰岛素依赖型糖尿病大鼠中apoB mRNA编辑增强，这可能导致血浆apoB-48水平升高。
