一项最新研究表明，SOCS家族的SOCS-7蛋白与葡萄糖代谢以及胰岛素表达有密切关系，缺失SOCS-7蛋白可以增加胰岛素敏感性。这项研究结果即将发表在9月1日的《临床研究》杂志上。
胰岛素抵抗是导致非胰岛素依赖型糖尿病的一个最基本的致病因素。通过减少胰岛素受体底物(IRS)蛋白的水平能够增加胰岛素受体活性时间、炎症时间和胰岛素水平，从而有助于降低胰岛素抵抗程度。目前，对胰岛素受体底物(IRS)蛋白失活和继发的胰岛素抵抗的发生机制尚不清楚。SOCS家族的蛋白已经应用于胰岛素水平的负性调节，还可以通过蛋白质降解体（proteasome）降解靶标蛋白来调节细胞因子信号。特别指出的是，SOCS-7蛋白的功能还不是很清楚。
研究负责人、Iowa大学的Paul Rothman博士和同事指出，“SOCS-7蛋白与胰岛素信号层联系统的主要成分有密切联系，可以对胰岛素信号水平进行调节。”
研究人员培育了SOCS-7蛋白缺失小鼠模型。动物研究发现，SOCS-7蛋白的缺失会增加IRS蛋白的水平，延长IRS的活性。葡萄糖耐量试验和胰岛素耐量试验证明，SOCS-7蛋白缺失的小鼠具有更高的胰岛素敏感性。另外，SOCS-7蛋白缺失的小鼠胰岛的生长水平增加、餐前胰岛素水平增加和饥饿性低血糖发生风险增加。
研究人员表示，“我们通过SOCS-7蛋白基因敲除小鼠模型所表现的增强的胰岛素敏感性的特点可以得知，SOCS-7是调节葡萄糖代谢平衡和胰岛素表达信号的重要的调节因子。”
小知识：
有关SOCS7 蛋白的特性：
SOCS7 Suppressor of cytokine signaling 7 NAP4, NAP-4, Nck-associated protein 4, SOCS6, SOCS-7, suppressor of cytokine signaling 7 Homo sapiens
UniProt O14512, O14512
OMIM 608788
NCBI Gene 30837
NCBI RefSeq NP_055413
NCBI RefSeq NM_014598
NCBI Accession AB005216, BAA22432, O14512
原文报道：
Insulin resistance is a fundamental factor in non-insulin-dependent diabetes. Prolonged activation of the insulin receptor, inflammation, and excessive insulin levels can induce insulin resistance by decreasing levels of insulin receptor substrate (IRS) proteins. However, the mechanism(s) underlying the destruction of IRS proteins and subsequent resistance to insulin have not been well defined. Proteins of the SOCS family have been implicated in the negative regulation of insulin signaling and also regulate cytokine signaling by targeting proteins for degradation by the proteasome. In particular, the function for the SOCS-7 protein was previously unclear.
In a study appearing online on August 25 in advance of print publication of the September 1 issue of the Journal of Clinical Investigation, Paul Rothman and colleagues from the University of Iowa demonstrate that SOCS-7 regulates insulin signaling by associating with several components of the insulin-signaling cascade.
The researchers generate SOCS-7-deficient mice and show that cells lacking SOCS-7 have increased IRS protein levels and prolonged IRS activation. SOCS-7 deficient mice are more insulin sensitive as measured by a glucose tolerance test and an insulin tolerance test. In addition, SOCS-7-deficient mice exhibit increased growth of pancreatic islets with increased fasting insulin levels and hypoglycemia. As one of the only mouse knockout models featuring increased insulin sensitivity, these data suggest that SOCS-7 is a potent regulator of glucose homeostasis and insulin signaling.
TITLE: Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of langerhans
AUTHOR:
Paul B. Rothman
University of Iowa, Iowa City, IA USA
View the PDF of this article at:
https://www.the-jci.org/article.php?id=23853
