Zhu Chaoyu, Xiao Yuanyuan, Liu Xiaohua, Han Junfeng, Zhang Jianmei, Wei Li, Jia Weiping
Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai, China.
Cell Physiol Biochem. 2015;35(2):778-88. doi: 10.1159/000369737. Epub 2015 Jan 30.
BACKGROUND/AIMS: Pioglitazone, a peroxisome proliferator-activated receptor γ activator, is clinically used to treat insulin resistance. However, the underlying mechanism of pioglitazone's action remains unclear. We investigated whether, and how, pioglitazone modulates serum level of retinol binding protein 4 (RBP4), an adipocytokine associated with obesity and insulin resistance.
Insulin sensitivity was determined by oral glucose tolerance test, and RBP4 expression was detected by RT-PCR and Western blotting.
Pioglitazone treatment significantly decreased serum RBP4 levels in obese rats, which was correlated with reduced body weight and increased insulin sensitivity. Moreover, pioglitazone greatly decreased RBP4 mRNA and protein levels in adipose tissue but not in the liver. Consistently, pioglitazone treatment significantly reduced RBP4 protein expression in 3T3-L1 adipocytes but not in HepG2 cells.
These results demonstrate that pioglitazone inhibits the level of serum RPB4 by suppressing RBP4 expression in adipose tissue of obese rats, suggesting that inhibiting RBP4 expression in adipocytes may provide a mechanism by which pioglitazone improves insulin sensitivity in insulin-resistant subjects.
背景/目的:吡格列酮是一种过氧化物酶体增殖物激活受体γ激动剂,临床上用于治疗胰岛素抵抗。然而,吡格列酮作用的潜在机制仍不清楚。我们研究了吡格列酮是否以及如何调节视黄醇结合蛋白4(RBP4)的血清水平,RBP4是一种与肥胖和胰岛素抵抗相关的脂肪细胞因子。
通过口服葡萄糖耐量试验测定胰岛素敏感性,通过逆转录-聚合酶链反应(RT-PCR)和蛋白质印迹法检测RBP4表达。
吡格列酮治疗显著降低了肥胖大鼠的血清RBP4水平,这与体重减轻和胰岛素敏感性增加相关。此外,吡格列酮显著降低了脂肪组织中RBP4的mRNA和蛋白质水平,但对肝脏无此作用。同样,吡格列酮治疗显著降低了3T3-L1脂肪细胞中RBP4蛋白的表达,但对HepG2细胞无此作用。
这些结果表明,吡格列酮通过抑制肥胖大鼠脂肪组织中RBP4的表达来降低血清RPB4水平,提示抑制脂肪细胞中RBP4的表达可能是吡格列酮改善胰岛素抵抗患者胰岛素敏感性的一种机制。