Inukai Kouichi, Nakashima Youhei, Watanabe Masaki, Kurihara Susumu, Awata Takuya, Katagiri Hideki, Oka Yoshitomo, Katayama Shigehiro
The Fourth Department of Internal Medicine, Saitama Medical School, Morohongo 38, Moroyama, Iruma-gun, Saitama 350-0495, Japan.
Biochem Biophys Res Commun. 2004 May 14;317(4):1075-9. doi: 10.1016/j.bbrc.2004.03.151.
Angiopoietin-like protein 3 (ANGPTL3) is secreted by the liver and was recently postulated to be an important hormone regulating serum triglyceride levels. In the present study, in order to clarify the regulation of ANGPTL3 gene expression in diabetic states, we examined mRNA and protein levels of ANGPTL3 in the livers of diabetic animals. The level of ANGPTL3 mRNA was increased approximately 2.2-fold in the livers of streptozotocin (STZ) diabetic mice, and this effect was reversed by administration of insulin. Furthermore, the level of ANGPTL3 mRNA was increased more than 3.0-fold in type 2 diabetic obese mice, db/db mice, as compared with age matched lean littermates. The hepatic level of ANGPTL3 protein was also increased in these diabetic mice to an extent similar to that of ANGPTL3 mRNA. Thus, the expression of ANGPTL3 was enhanced in both insulin-deficient and -resistant diabetic states. These results strongly suggest ANGPTL3 to play an important role in hyperlipidemia in diabetes.
血管生成素样蛋白3（ANGPTL3）由肝脏分泌，最近被认为是一种调节血清甘油三酯水平的重要激素。在本研究中，为了阐明糖尿病状态下ANGPTL3基因表达的调控机制，我们检测了糖尿病动物肝脏中ANGPTL3的mRNA和蛋白质水平。链脲佐菌素（STZ）诱导的糖尿病小鼠肝脏中ANGPTL3 mRNA水平增加了约2.2倍，胰岛素给药可逆转这一效应。此外，与年龄匹配的瘦型同窝小鼠相比，2型糖尿病肥胖小鼠（db/db小鼠）肝脏中ANGPTL3 mRNA水平增加了3倍以上。这些糖尿病小鼠肝脏中ANGPTL3蛋白水平也增加到与ANGPTL3 mRNA相似的程度。因此，在胰岛素缺乏和抵抗的糖尿病状态下，ANGPTL3的表达均增强。这些结果强烈表明ANGPTL3在糖尿病高脂血症中起重要作用。
