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胰岛素抵抗与循环视黄醇结合蛋白及蛋白C抑制剂无关。

Insulin resistance is unrelated to circulating retinol binding protein and protein C inhibitor.

作者信息

Promintzer Miriam, Krebs Michael, Todoric Jelena, Luger Anton, Bischof Martin Georg, Nowotny Peter, Wagner Oswald, Esterbauer Harald, Anderwald Christian

机构信息

Department of Internal Medicine III, Medical University of Vienna, A-1090 Vienna, Austria.

出版信息

J Clin Endocrinol Metab. 2007 Nov;92(11):4306-12. doi: 10.1210/jc.2006-2522. Epub 2007 Aug 28.

Abstract

CONTEXT

Recent data suggest that circulating retinol-binding protein (RBP) might be involved in the pathogenesis of insulin resistance. Moreover, protein C inhibitor (PCI), which specifically binds retinoic acid, was found to be increased in myocardial infarction survivors who are also insulin resistant.

OBJECTIVE

The objective of this study was to investigate the association of insulin resistance with RBP factors and PCI active antigen.

DESIGN AND SETTING

This was a clinical study.

PATIENTS

Nondiabetic humans with high (IS; n = 20, 14 females, six males, aged 47.2 +/- 1.9 yr, body mass index 26 +/- 1 kg/m(2)) and low (IR; n = 20, 14 females, six males, aged 45.5 +/- 1.7 yr, body mass index 28 +/- 1 kg/m(2)) insulin-stimulated glucose-disposal (M) participated in this study.

MAIN OUTCOME MEASURES

M was measured by 2-h hyperinsulinemic (40 mU.min(-1).m(-2))-isoglycemic clamp tests. Measurements of RBP were performed using a nephelometric method and validated using quantitative Western blotting.

RESULTS

M (80-120 min) was higher in IS (10.9 +/- 0.6 mg.min(-1).kg(-1)) than IR (4.0 +/- 0.2; P < 10(-12)). Fasting plasma RBP concentrations were comparable between IS and IR measured by both nephelometry (IS: 4.4 +/- 0.3; IR: 4.6 +/- 0.3 mg/dl, P = 0.6) and quantitative Western blot (IS 7.9 +/- 0.5, IR 8.3 +/- 0.6 mg/dl; P = 0.6). Fasting plasma PCI active antigen was similar in both groups. Plasma RBP and PCI were not significantly related to M. RBP was positively correlated with uric acid (r = 0.488, P = 0.003), triglycerides (r = 0.592, P < 0.001), prealbumin (r = 0.63, P < 0.0001), and vitamin A (r = 0.75, P < 10(-6)).

CONCLUSIONS

Our data demonstrate that healthy, insulin-resistant humans do not show altered plasma retinol binding factors, such as RBP and PCI. Both do not significantly correlate with insulin sensitivity. Thus, our findings do not support the hypothesis of insulin sensitivity modulation by proteins involved in retinol transport.

摘要

背景

近期数据表明,循环视黄醇结合蛋白(RBP)可能参与胰岛素抵抗的发病机制。此外,发现特异性结合视黄酸的蛋白C抑制剂(PCI)在同样存在胰岛素抵抗的心肌梗死幸存者中升高。

目的

本研究的目的是调查胰岛素抵抗与RBP因子和PCI活性抗原之间的关联。

设计与地点

这是一项临床研究。

患者

胰岛素刺激的葡萄糖处置(M)高(IS组;n = 20,14名女性,6名男性,年龄47.2±1.9岁,体重指数26±1 kg/m²)和低(IR组;n = 20,14名女性,6名男性,年龄45.5±1.7岁,体重指数28±1 kg/m²)的非糖尿病患者参与了本研究。

主要观察指标

通过2小时高胰岛素血症(40 mU·min⁻¹·m⁻²)-等血糖钳夹试验测量M。使用散射比浊法测量RBP,并通过定量蛋白质免疫印迹法进行验证。

结果

IS组(10.9±0.6 mg·min⁻¹·kg⁻¹)在80 - 120分钟时的M高于IR组(4.0±0.2;P < 10⁻¹²)。通过散射比浊法(IS组:4.4±0.3;IR组:4.6±0.3 mg/dl,P = 0.6)和定量蛋白质免疫印迹法(IS组7.9±0.5,IR组8.3±0.6 mg/dl;P = 0.6)测量,IS组和IR组的空腹血浆RBP浓度相当。两组的空腹血浆PCI活性抗原相似。血浆RBP和PCI与M无显著相关性。RBP与尿酸(r = 0.488,P = 0.003)、甘油三酯(r = 0.592,P < 0.001)、前白蛋白(r = 0.63,P < 0.0001)和维生素A(r = 0.75,P < 10⁻⁶)呈正相关。

结论

我们的数据表明,健康的胰岛素抵抗人群血浆中视黄醇结合因子如RBP和PCI没有改变。两者均与胰岛素敏感性无显著相关性。因此,我们的研究结果不支持视黄醇转运相关蛋白调节胰岛素敏感性的假说。

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