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胰岛素调节成熟3T3-L1脂肪细胞中蛋白质的分泌:加工过程转录调控的作用。

Insulin modulates the secretion of proteins from mature 3T3-L1 adipocytes: a role for transcriptional regulation of processing.

作者信息

Wang P, Keijer J, Bunschoten A, Bouwman F, Renes J, Mariman E

机构信息

Functional Genomics Group, Research Institute NUTRIM, Department of Human Biology, Maastricht University, Maastricht, The Netherlands.

出版信息

Diabetologia. 2006 Oct;49(10):2453-62. doi: 10.1007/s00125-006-0321-5. Epub 2006 Aug 4.

Abstract

AIMS/HYPOTHESIS: Under conditions of insulin resistance and type 2 diabetes, fat cells are subjected to increased levels of insulin, which may have a major impact on the secretion of adipokines.

MATERIALS AND METHODS

Using transcriptomics and proteomics, we investigated how insulin affects the transcription and protein secretion profile of mature 3T3-L1 adipocytes.

RESULTS

We found that insulin has a significant impact on protein secretion of 3T3-L1 adipocytes. However, transcription is not the major regulation point for these secreted proteins. For extracellular matrix components, our data suggest that the mRNA level of processing enzymes, but not of target proteins, is the regulating point at which insulin stimulates secretion and function of the relevant proteins. Among these enzymes, we report a novel finding, namely that sulfatase 2 gene is regulated by insulin, which may induce a functional change in cultured adipocytes.

CONCLUSIONS/INTERPRETATION: We propose that enhancement of protein processing and secretion rather than transcription of the secreted protein genes is part of the strategic role of insulin in the induction of cellular responses.

摘要

目的/假设:在胰岛素抵抗和2型糖尿病的情况下,脂肪细胞会受到更高水平胰岛素的影响,这可能对脂肪因子的分泌产生重大影响。

材料与方法

我们运用转录组学和蛋白质组学技术,研究胰岛素如何影响成熟3T3-L1脂肪细胞的转录和蛋白质分泌谱。

结果

我们发现胰岛素对3T3-L1脂肪细胞的蛋白质分泌有显著影响。然而,转录并非这些分泌蛋白的主要调控点。对于细胞外基质成分,我们的数据表明,加工酶的mRNA水平而非靶蛋白的mRNA水平是胰岛素刺激相关蛋白分泌和功能的调控点。在这些酶中,我们有一项新发现,即硫酸酯酶2基因受胰岛素调控,这可能会在培养的脂肪细胞中引发功能变化。

结论/解读:我们提出,增强蛋白质加工和分泌而非分泌蛋白基因的转录是胰岛素在诱导细胞反应中的战略作用的一部分。

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