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全反式视黄酸降低糖尿病小鼠血清视黄醇结合蛋白 4 浓度并增加胰岛素敏感性。

All-trans retinoic acid lowers serum retinol-binding protein 4 concentrations and increases insulin sensitivity in diabetic mice.

机构信息

Laboratory of Nutrition and Cancer, Centre de recherché du Centre hospitalier de l'Université de Montréal-Hôtel-Dieu; Department of Medicine, Université de Montréal, Montreal, H2W 1T7, Canada.

出版信息

J Nutr. 2010 Feb;140(2):311-6. doi: 10.3945/jn.109.115147. Epub 2009 Dec 23.

DOI:10.3945/jn.109.115147
PMID:20032483
Abstract

Recent investigations have demonstrated that elevated serum retinol-binding protein 4 (RBP4) secreted from adipose tissue plays a role in the development of systemic insulin resistance, and lowering RBP4 improves insulin sensitivity. These observations provide a rationale for the development of new antidiabetic agents aimed at reducing serum RBP4 concentrations. In this study, we sought to determine whether retinoic acid (RA) administration decreases serum RBP4 and suppresses insulin resistance in diabetic ob/ob mice. All-trans RA [100 mug/(moused) in corn oil] was administered by stomach intubation to a group of ob/ob mice, with the control group receiving the vehicle for 16 d. Body weight and food intake were monitored. Glucose and insulin tolerance tests were performed. We quantified serum RBP4 and retinol by Western blotting and HPLC, respectively. RA treatment reduced body weight (P < 0.05), basal serum glucose (P < 0.001), serum retinol (P < 0.01), and RBP4 (P < 0.05). It improved insulin sensitivity and decreased the retinol:RBP4 ratio (P < 0.05). These studies suggest that RA is an effective antidiabetic agent that could be considered in the treatment of type 2 diabetes.

摘要

最近的研究表明,脂肪组织分泌的高血清视黄醇结合蛋白 4(RBP4)在全身胰岛素抵抗的发展中起作用,降低 RBP4 可改善胰岛素敏感性。这些观察结果为开发旨在降低血清 RBP4 浓度的新型抗糖尿病药物提供了依据。在这项研究中,我们试图确定视黄酸(RA)是否可以降低血清 RBP4 并抑制糖尿病 ob/ob 小鼠的胰岛素抵抗。全反式 RA(100 微克/(只小鼠)在玉米油中)通过胃内插管给予一组 ob/ob 小鼠,对照组接受载体 16 天。监测体重和食物摄入量。进行葡萄糖和胰岛素耐量试验。我们分别通过 Western blot 和 HPLC 定量血清 RBP4 和视黄醇。RA 治疗可降低体重(P < 0.05)、基础血清葡萄糖(P < 0.001)、血清视黄醇(P < 0.01)和 RBP4(P < 0.05)。它改善了胰岛素敏感性并降低了视黄醇:RBP4 比值(P < 0.05)。这些研究表明,RA 是一种有效的抗糖尿病药物,可考虑用于治疗 2 型糖尿病。

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