Department of Pathology, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.
Endocr J. 2010;57(10):881-93. doi: 10.1507/endocrj.k10e-043. Epub 2010 Aug 17.
The "lipotoxicity" hypothesis holds that fat-induced hepatic insulin resistance (FIHIR) may play a major role in the pathogenesis of type 2 diabetes. Berberine has been reported to have antidiabetic properties. However, the molecular mechanisms for this action are not fully clarified. Therefore, we will investigate the gene expression alterations involved in the therapeutic effect of berberine on FIHIR in diabetic hamsters and possible mechanisms. In this study, type 2 diabetic hamsters were induced by high-fat diet with streptozotocin injection. After 9 weeks of berberine-treatment, the gene expression alterations involved in the therapeutic molecular mechanisms of berberine on FIHIR will be studied by microarray technology and real time RT-PCR. Our study demonstrates berberine significantly improved fat-induced insulin resistance and diabetic phenotype in type 2 diabetic hamsters. The alterations of certain metabolism related genes and their main regulators: Liver X receptor (LXR) α, Peroxisome proliferator-activated receptor (PPAR) α and Sterol regulatory element-binding protein (SREBPs) are observed in the liver of treated and untreated diabetic hamsters. Compared with diabetic hamsters, the increased mRNA levels of LXRα and PPARα and the decreased mRNA levels of SREBPs are observed in berberine-treated diabetic hamster. The statistical significance of the expression of hepatic LXRα, SREBPs and PPARα and their certain target genes is found between treated and untreated diabetic hamsters. These results suggest that altered hepatic SREBPs, LXRα and PPARα transcriptional programs possibly involve in the therapeutic mechanisms of berberine on FIHIR in type 2 diabetic hamsters.
“脂毒性”假说认为，脂肪诱导的肝胰岛素抵抗（FIHIR）可能在 2 型糖尿病的发病机制中起主要作用。小檗碱已被报道具有抗糖尿病作用。然而，这种作用的分子机制尚未完全阐明。因此，我们将研究小檗碱治疗糖尿病仓鼠 FIHIR 的疗效所涉及的基因表达变化及其可能的机制。在这项研究中，通过高脂肪饮食联合链脲佐菌素注射诱导 2 型糖尿病仓鼠。在小檗碱治疗 9 周后，通过微阵列技术和实时 RT-PCR 研究小檗碱治疗 FIHIR 的治疗分子机制所涉及的基因表达变化。我们的研究表明，小檗碱可显著改善 2 型糖尿病仓鼠的脂肪诱导胰岛素抵抗和糖尿病表型。在未经治疗和治疗的糖尿病仓鼠的肝脏中观察到某些代谢相关基因及其主要调节剂的变化：肝 X 受体（LXR）α、过氧化物酶体增殖物激活受体（PPAR）α 和固醇调节元件结合蛋白（SREBPs）。与糖尿病仓鼠相比，小檗碱治疗的糖尿病仓鼠中 LXRα 和 PPARα 的 mRNA 水平升高，而 SREBPs 的 mRNA 水平降低。在治疗和未治疗的糖尿病仓鼠之间，发现肝 LXRα、SREBPs 和 PPARα 及其某些靶基因的表达具有统计学意义。这些结果表明，改变的肝 SREBPs、LXRα 和 PPARα 转录程序可能涉及小檗碱治疗 2 型糖尿病仓鼠 FIHIR 的治疗机制。
