Mizutani N, Ozaki N, Seino Y, Fukami A, Sakamoto E, Fukuyama T, Sugimura Y, Nagasaki H, Arima H, Oiso Y
Department of Endocrinology and Diabetes, Field of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Exp Clin Endocrinol Diabetes. 2012 Mar;120(3):139-44. doi: 10.1055/s-0031-1291258. Epub 2011 Nov 8.
Angiopoietin-like protein 4 (Angptl4) is thought to cause an increase in serum triglyceride levels. In the present study, we elucidated Angptl4 expression in the mouse models of type 1 and type 2 diabetes mellitus, and investigated the possible mechanisms involved.
Type 1 diabetes was induced in C57BL/6 J mice by treating them with streptozotocin (STZ). Type 2 diabetes was induced by feeding the mice a high-fat diet (HFD) for 18 weeks.
The levels of Angptl4 mRNA expression in liver, white adipose tissue (WAT), and brown adipose tissue (BAT) were found to increase in the STZ diabetic mice relative to control mice. This effect was attenuated by insulin administration. In the HFD diabetic mice, the Angptl4 mRNA expression levels were increased in liver, WAT, and BAT. Treatment with metformin for 4 weeks attenuated the increased levels of Angptl4 mRNA. Fatty acids (FAs) such as palmitate and linoleate induced Angptl4 mRNA expression in H4IIE hepatoma cells and 3T3-L1 adipocytes. Treatment with insulin but not metformin attenuated FA-induced Angptl4 mRNA expression in H4IIE. Both insulin and metformin did not influence the effect of FAs in 3T3-L1 cells.
These observations demonstrated that Angptl4 mRNA expression was increased through the elevated free FAs in diabetic mice.
血管生成素样蛋白4（Angptl4）被认为会导致血清甘油三酯水平升高。在本研究中，我们阐明了1型和2型糖尿病小鼠模型中Angptl4的表达情况，并研究了其中可能涉及的机制。
通过给C57BL/6 J小鼠注射链脲佐菌素（STZ）诱导1型糖尿病。通过给小鼠喂食高脂饮食（HFD）18周诱导2型糖尿病。
相对于对照小鼠，STZ诱导的糖尿病小鼠肝脏、白色脂肪组织（WAT）和棕色脂肪组织（BAT）中的Angptl4 mRNA表达水平升高。胰岛素给药可减弱这种作用。在HFD诱导的糖尿病小鼠中，肝脏、WAT和BAT中的Angptl4 mRNA表达水平升高。用二甲双胍治疗4周可减弱Angptl4 mRNA水平的升高。棕榈酸和亚油酸等脂肪酸可诱导H4IIE肝癌细胞和3T3-L1脂肪细胞中Angptl4 mRNA的表达。胰岛素治疗而非二甲双胍治疗可减弱H4IIE中脂肪酸诱导的Angptl4 mRNA表达。胰岛素和二甲双胍均不影响3T3-L1细胞中脂肪酸的作用。
这些观察结果表明，糖尿病小鼠中Angptl4 mRNA表达通过游离脂肪酸升高而增加。
