Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Eur J Clin Invest. 2016 Jun;46(6):535-43. doi: 10.1111/eci.12629. Epub 2016 Apr 30.
Secreted frizzled-related protein (Sfrp)5 improves insulin sensitivity, but impairs beta-cell function in rodents. However, the relationship between Sfrp5, insulin sensitivity and secretion in humans is currently unclear. Therefore, the aim of the study was to characterize the associations between serum Sfrp5 and indices of insulin sensitivity and beta-cell function from dynamic measurements using oral glucose tolerance tests (OGTT) in humans.
This study enrolled 194 individuals with nonalcoholic fatty liver disease (NAFLD), who were diagnosed based on ultrasound and liver transaminases and underwent a frequent sampling 75-g OGTT. Fasting serum Sfrp5 was measured by ELISA. Associations were assessed with several indices of insulin sensitivity and beta-cell function derived from glucose, insulin and C-peptide concentrations during the OGTT.
Circulating Sfrp5 associated inversely with the insulinogenic index based on C-peptide (rs = -0·244, P = 0·001), but not with the insulinogenic index based on insulin levels (rs = -0·007, P = 0·926) after adjustment for age, sex and body mass index. Sfrp5 inversely correlated only with QUICKI as a marker of insulin sensitivity in the model adjusted for age and sex (rs = -0·149, P = 0·039). These associations were not influenced by the additional adjustment for hepatic steatosis index.
The inverse association of serum Sfrp5 with beta-cell function suggests a detrimental role of Sfrp5 for insulin secretion also in humans. The severity of NAFLD does not appear to affect this relationship. The weak association between serum Sfrp5 and insulin sensitivity was partially explained by body mass.
分泌卷曲相关蛋白 5（Sfrp5）可改善胰岛素敏感性，但会损害啮齿动物的胰岛β细胞功能。然而，目前尚不清楚 Sfrp5、胰岛素敏感性和人类胰岛β细胞功能之间的关系。因此，本研究旨在通过口服葡萄糖耐量试验（OGTT）的动态测量，描述血清 Sfrp5 与胰岛素敏感性和胰岛β细胞功能指标之间的关系。
本研究纳入了 194 名非酒精性脂肪性肝病（NAFLD）患者，这些患者根据超声和肝转氨酶诊断，并进行了频繁采样 75g OGTT。采用 ELISA 法检测空腹血清 Sfrp5。通过 OGTT 期间葡萄糖、胰岛素和 C 肽浓度来评估与多种胰岛素敏感性和胰岛β细胞功能指标的相关性。
循环 Sfrp5 与 C 肽的胰岛素原指数呈负相关（rs = -0·244，P = 0·001），但与胰岛素的胰岛素原指数呈负相关（rs = -0·007，P = 0·926），调整年龄、性别和体重指数后。在调整年龄和性别后，Sfrp5 仅与 QUICKI 呈负相关，作为胰岛素敏感性的标志物（rs = -0·149，P = 0·039）。这些关联不受肝脂肪变性指数的额外调整影响。
血清 Sfrp5 与胰岛β细胞功能呈负相关，表明 Sfrp5 对胰岛素分泌也具有有害作用，在人类中也是如此。NAFLD 的严重程度似乎不会影响这种关系。血清 Sfrp5 与胰岛素敏感性之间的弱相关性部分由体重解释。
