Broch Montserrat, Vendrell Joan, Ricart Wifredo, Richart Cristóbal, Fernández-Real José-Manuel
Reseach Unit, Pere Virgili Institute for Biomedical Research, Tarragona, Spain.
Diabetes Care. 2007 Jul;30(7):1802-6. doi: 10.2337/dc06-2034. Epub 2007 Apr 6.
Recent investigations disclosed an upregulation of retinol-binding protein-4 (RBP4) in the adipose tissue of several insulin-resistant mouse models and increased serum RBP4 concentration in subjects with obesity and type 2 diabetes in association with insulin resistance. There is some experimental evidence that RBP4 also could been linked to insulin secretion.
We aimed to evaluate insulin secretion, insulin sensitivity, insulin disposition index (minimal model analysis), and circulating RBP4 (enzyme-linked immunosorbent assay) in nondiabetic men with a wide range of obesity (n = 107).
Serum RBP4 concentration was nonsignificantly different among lean, overweight, and obese subjects. Circulating RBP4 was not associated with age, BMI, waist-to-hip ratio, or metabolic parameters, including insulin sensitivity (r = -0.03, P = 0.6). On the contrary, circulating RBP4 was negatively associated with insulin secretion, especially in obese subjects (r = -0.48, P = 0.007), in whom RBP4 also was linked to insulin disposition index (r = -0.44, P = 0.01). On multiple regression analyses to predict insulin secretion (acute insulin response [AIR(g)]), insulin sensitivity was the only factor that contributed to 17% of AIR(g) variance in nonobese subjects. In obese subjects, however, RBP4 emerged as an independent factor that contributed independently to AIR(g) variance (23%).
Our results suggest that oversecretion of RBP4 may negatively affect beta-cell function directly or by preventing the binding of transthyretin to its receptor. These mechanisms could be behind the association between increased circulating RBP4 and type 2 diabetes. RBP4 could be one signal from insulin-resistant tissues that impacts on beta-cell secretion.
近期研究发现，在几种胰岛素抵抗小鼠模型的脂肪组织中，视黄醇结合蛋白4（RBP4）上调，肥胖和2型糖尿病患者血清RBP4浓度升高，且与胰岛素抵抗相关。有一些实验证据表明，RBP4也可能与胰岛素分泌有关。
我们旨在评估肥胖程度各异的非糖尿病男性（n = 107）的胰岛素分泌、胰岛素敏感性、胰岛素处置指数（最小模型分析）以及循环RBP4（酶联免疫吸附测定）。
血清RBP4浓度在瘦、超重和肥胖受试者之间无显著差异。循环RBP4与年龄、体重指数、腰臀比或代谢参数无关，包括胰岛素敏感性（r = -0.03，P = 0.6）。相反，循环RBP4与胰岛素分泌呈负相关，尤其是在肥胖受试者中（r = -0.48，P = 0.007），在这些受试者中，RBP4也与胰岛素处置指数相关（r = -0.44，P = 0.01）。在预测胰岛素分泌（急性胰岛素反应[AIR(g)]）的多元回归分析中，胰岛素敏感性是导致非肥胖受试者AIR(g)变异17%的唯一因素。然而，在肥胖受试者中，RBP4成为独立因素，对AIR(g)变异有独立贡献（23%）。
我们的结果表明，RBP4分泌过多可能直接或通过阻止甲状腺素转运蛋白与其受体结合而对β细胞功能产生负面影响。这些机制可能是循环RBP4升高与2型糖尿病之间关联的背后原因。RBP4可能是来自胰岛素抵抗组织的影响β细胞分泌的一个信号。
