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高血糖对人正常腹膜和粘连成纤维细胞中胰岛素及胰岛素样生长因子-I受体差异表达的影响。

Effects of hyperglycemia on the differential expression of insulin and insulin-like growth factor-I receptors in human normal peritoneal and adhesion fibroblasts.

作者信息

Rizk Natalie N, Saed Ghassan M, Diamond Michael P

机构信息

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan 48201, USA.

出版信息

Fertil Steril. 2006 Oct;86(4 Suppl):1217-22. doi: 10.1016/j.fertnstert.2006.04.022. Epub 2006 Sep 7.

Abstract

OBJECTIVE

To determine whether the insulin receptor (IR), insulin-like growth factor-I receptor (IGF-IR), and IGF-I are expressed differentially in fibroblasts isolated from normal peritoneal and adhesion tissue before and after 24-hour treatment with increasing glucose concentrations.

DESIGN

Prospective experimental study.

SETTING

University medical center.

PATIENT(S): Primary cultures of fibroblasts established from peritoneal and adhesion tissues of the same patients.

INTERVENTION(S): Glucose treatment of the primary cultured fibroblasts for 24 hours with increasing concentrations of glucose (100-850 mg/dL).

MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction was used to measure messenger RNA (mRNA) levels for IR, IGF-IR, and IGF-I. Enzyme-linked immunosorbent assay was used to determine protein levels.

RESULT(S): At the normal glycemic level (100 mg/dL), adhesion fibroblasts have significantly higher mRNA levels of the IR (7.96 +/- 0.15 vs. 6.97 +/- 0.16; P<.05), IGF-IR (7.72 +/- 0.22 vs. 6.88 +/- 0.06; P<.05), and IGF-I (7.04 +/- 0.10 vs. 5.92 +/- 0.10; P<.05) when compared with normal fibroblasts, respectively. Data are expressed as log(mRNA/microg RNA). Normal fibroblasts respond to increasing glucose concentrations by increasing the expression levels of the IR, IGF-IR, and IGF-I, whereas adhesion fibroblasts respond by decreasing the expression of the IR, IGF-IR, and IGF-I.

CONCLUSION(S): The differential expression of the IR, IGF-IR, and IGF-I in adhesion fibroblasts may contribute to the pathogenesis of fibrosis observed in diabetic patients.

摘要

目的

确定在正常腹膜组织和粘连组织分离出的成纤维细胞中,胰岛素受体(IR)、胰岛素样生长因子-I受体(IGF-IR)和IGF-I在葡萄糖浓度递增处理24小时前后是否存在差异表达。

设计

前瞻性实验研究。

地点

大学医学中心。

患者

从同一患者的腹膜和粘连组织建立的成纤维细胞原代培养物。

干预措施

用浓度递增的葡萄糖(100 - 850mg/dL)对原代培养的成纤维细胞进行24小时处理。

主要观察指标

采用实时聚合酶链反应测量IR、IGF-IR和IGF-I的信使核糖核酸(mRNA)水平。采用酶联免疫吸附测定法测定蛋白质水平。

结果

在正常血糖水平(100mg/dL)时,与正常成纤维细胞相比,粘连成纤维细胞的IR(7.96±0.15对6.97±0.16;P<0.05)、IGF-IR(7.72±0.22对6.88±0.06;P<0.05)和IGF-I(7.04±0.10对5.92±0.10;P<0.05)的mRNA水平分别显著更高。数据以log(mRNA/μg RNA)表示。正常成纤维细胞对葡萄糖浓度增加的反应是增加IR、IGF-IR和IGF-I的表达水平,而粘连成纤维细胞的反应是降低IR、IGF-IR和IGF-I的表达。

结论

粘连成纤维细胞中IR、IGF-IR和IGF-I的差异表达可能有助于解释糖尿病患者中观察到的纤维化发病机制。

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