Yagmur Eray, Weiskirchen Ralf, Gressner Axel M, Trautwein Christian, Tacke Frank
Institute of Clinical Chemistry and Pathobiochemistry, RWTH-University Hospital Aachen, 52074 Aachen, Germany.
Diabetes Care. 2007 May;30(5):1168-72. doi: 10.2337/dc06-2323. Epub 2007 Mar 2.
Retinol-binding protein 4 (RBP4) has been identified as a novel adipokine mediating systemic insulin resistance, and elevated serum RBP4 indicates overt or impending insulin resistance in lean, obese, and type 2 diabetic subjects. As insulin resistance is present in nearly all patients with liver cirrhosis, we evaluated RBP4 in patients with chronic liver disease (CLD).
Serum RBP4 was measured in 111 CLD patients. Ninety-nine age- and sex-matched healthy blood donors served as control subjects. RBP4 gene expression was also quantified in normal and cirrhotic rat liver.
In CLD patients, serum RBP4 was significantly reduced compared with healthy control subjects and closely correlated with the stage of liver cirrhosis. CLD patients without cirrhosis showed normal RBP4 concentrations, which correlated with serum glucose and insulin secretion and inversely correlated with insulin sensitivity. In patients with Child A-C liver cirrhosis, however, RBP4 was not correlated with glucose metabolism or other adipokines, such as adiponectin or resistin, but closely linked to the hepatic biosynthetic capacity, fibrotic changes in liver histology, or clinical complications such as portal hypertension. In an animal model of experimental cirrhosis, hepatic RBP4 gene expression decreased in cirrhotic liver.
RBP4 appears, unlike in obesity or type 2 diabetes, not to be a relevant systemic factor in the pathogenesis of insulin resistance in liver cirrhosis. Liver function has a tremendous impact on RBP4 levels, and future studies will need to take liver function into account when examining serum RBP4 levels.
视黄醇结合蛋白4（RBP4）已被确认为一种介导全身胰岛素抵抗的新型脂肪因子，血清RBP4升高表明瘦人、肥胖者及2型糖尿病患者存在明显或即将出现的胰岛素抵抗。由于几乎所有肝硬化患者都存在胰岛素抵抗，我们对慢性肝病（CLD）患者的RBP4进行了评估。
检测了111例CLD患者的血清RBP4。99名年龄和性别匹配的健康献血者作为对照。还对正常和肝硬化大鼠肝脏中的RBP4基因表达进行了定量分析。
与健康对照相比，CLD患者血清RBP4显著降低，且与肝硬化分期密切相关。无肝硬化的CLD患者RBP4浓度正常，其与血清葡萄糖和胰岛素分泌相关，与胰岛素敏感性呈负相关。然而，在Child A - C级肝硬化患者中，RBP4与糖代谢或其他脂肪因子（如脂联素或抵抗素）无关，但与肝脏生物合成能力、肝脏组织学纤维化改变或门静脉高压等临床并发症密切相关。在实验性肝硬化动物模型中，肝硬化肝脏中肝脏RBP4基因表达降低。
与肥胖或2型糖尿病不同，RBP4似乎不是肝硬化胰岛素抵抗发病机制中的相关全身因素。肝功能对RBP4水平有巨大影响，未来在检测血清RBP4水平时需要考虑肝功能因素。
