Insulin regulates the unfolded protein response in human adipose tissue.
Insulin regulates the unfolded protein response in human adipose tissue.
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作者：
Boden G;Cheung P;Salehi S;Homko C;Loveland-Jones C;Jayarajan S;Stein TP;Williams KJ;Liu ML;Barrero CA;Merali S
内质网（ER）应激在肥胖中增加，被认为是许多肥胖相关病理的主要因素。对于导致肥胖人群内质网压力的原因，人们知之甚少。在这里，我们发现胰岛素上调了未折叠蛋白反应（UPR），这是一种对内质网络应激的适应性反应，在体外的3T3-L1脂肪细胞和体内的非糖尿病受试者的皮下脂肪组织中，胰岛素在整个生理胰岛素范围内（从~ 35到~ 1,450 pmol/L）依赖地增加了UPR剂量。胰岛素诱导的UPR不是由于葡萄糖摄取/代谢增加和氧化应激。然而，它与蛋白质合成的增加、泛素化相关蛋白的积累以及多种翻译后蛋白质修饰（乙酰化、甲基化、亚硝基化、琥珀酰化和泛素化）有关，其中一些是内质网应激的潜在原因。这些结果揭示了胰岛素的新的生理作用，并为肥胖中内质网应激的发展提供了可能的机制。它们也可能具有临床和治疗意义，例如，在用高剂量胰岛素治疗的糖尿病患者中。
Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be a major contributor to many obesity-related pathologies. Little is known about what causes ER stress in obese people. Here, we show that insulin upregulated the unfolded protein response (UPR), an adaptive reaction to ER stress, in vitro in 3T3-L1 adipocytes and in vivo, in subcutaneous (sc) adipose tissue of nondiabetic subjects, where it increased the UPR dose dependently over the entire physiologic insulin range (from ∼35 to ∼1,450 pmol/L). The insulin-induced UPR was not due to increased glucose uptake/metabolism and oxidative stress. It was associated, however, with increased protein synthesis, with accumulation of ubiquitination associated proteins, and with multiple posttranslational protein modifications (acetylations, methylations, nitrosylations, succinylation, and ubiquitinations), some of which are potential causes for ER stress. These results reveal a new physiologic role of insulin and provide a putative mechanism for the development of ER stress in obesity. They may also have clinical and therapeutic implications, e.g., in diabetic patients treated with high doses of insulin.
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影响因子：
3.5
作者：
Inageda, Kiyoshi
通讯作者：
Inageda, Kiyoshi
影响因子：
56.9
作者：
Lee, Ann-Hwee;Scapa, Erez F.;Glimcher, Laurie H.
通讯作者：
Glimcher, Laurie H.
影响因子：
62.1
作者：
Milne, Ginger L.;Yin, Huiyong;Hardy, Klarissa D.;Davies, Sean S.;Roberts, L. Jackson, II
通讯作者：
Roberts, L. Jackson, II
DOI：
10.1083/jcb.201003138
发表时间：
2010-05-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
Rutkowski DT;Hegde RS
通讯作者：
Hegde RS
影响因子：
3.7
作者：
Barrero CA;Datta PK;Sen S;Deshmane S;Amini S;Khalili K;Merali S
通讯作者：
Merali S