一項(xiàng)最新研究表明,，SOCS家族的SOCS-7蛋白與葡萄糖代謝以及胰島素表達(dá)有密切關(guān)系,，缺失SOCS-7蛋白可以增加胰島素敏感性,。這項(xiàng)研究結(jié)果即將發(fā)表在9月1日的《臨床研究》雜志上。
胰島素抵抗是導(dǎo)致非胰島素依賴型糖尿病的一個(gè)最基本的致病因素,。通過減少胰島素受體底物(IRS)蛋白的水平能夠增加胰島素受體活性時(shí)間,、炎癥時(shí)間和胰島素水平，從而有助于降低胰島素抵抗程度,。目前,，對(duì)胰島素受體底物(IRS)蛋白失活和繼發(fā)的胰島素抵抗的發(fā)生機(jī)制尚不清楚。SOCS家族的蛋白已經(jīng)應(yīng)用于胰島素水平的負(fù)性調(diào)節(jié),，還可以通過蛋白質(zhì)降解體（proteasome）降解靶標(biāo)蛋白來調(diào)節(jié)細(xì)胞因子信號(hào)。特別指出的是,，SOCS-7蛋白的功能還不是很清楚,。
研究負(fù)責(zé)人、Iowa大學(xué)的Paul Rothman博士和同事指出,，“SOCS-7蛋白與胰島素信號(hào)層聯(lián)系統(tǒng)的主要成分有密切聯(lián)系,，可以對(duì)胰島素信號(hào)水平進(jìn)行調(diào)節(jié),。”
研究人員培育了SOCS-7蛋白缺失小鼠模型。動(dòng)物研究發(fā)現(xiàn),，SOCS-7蛋白的缺失會(huì)增加IRS蛋白的水平,，延長IRS的活性。葡萄糖耐量試驗(yàn)和胰島素耐量試驗(yàn)證明,，SOCS-7蛋白缺失的小鼠具有更高的胰島素敏感性,。另外，SOCS-7蛋白缺失的小鼠胰島的生長水平增加,、餐前胰島素水平增加和饑餓性低血糖發(fā)生風(fēng)險(xiǎn)增加,。
研究人員表示，“我們通過SOCS-7蛋白基因敲除小鼠模型所表現(xiàn)的增強(qiáng)的胰島素敏感性的特點(diǎn)可以得知,，SOCS-7是調(diào)節(jié)葡萄糖代謝平衡和胰島素表達(dá)信號(hào)的重要的調(diào)節(jié)因子,。”
小知識(shí)：
有關(guān)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
原文報(bào)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
