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胰岛素抵抗的分子基础:胰岛素受体底物(IRS)和叉头框蛋白O1(Foxo1)在糖尿病及其并发症控制中的作用

Molecular Basis of Insulin Resistance: The Role of IRS and Foxo1 in the Control of Diabetes Mellitus and Its Complications.

作者信息

Guo Shaodong

机构信息

Division of Molecular Cardiology, Cardiovascular Research Institute, College of Medicine, Texas A&M University Health Science Center, Scott & White; Central Texas Veterans Health Care System, Temple, TX 76504, USA.

出版信息

Drug Discov Today Dis Mech. 2013 Jun 1;10(1-2):e27-e33. doi: 10.1016/j.ddmec.2013.06.003.

DOI:10.1016/j.ddmec.2013.06.003
PMID:24015152
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3763863/
Abstract

Insulin/IGF-1 signaling plays a central role in control of cellular metabolism and survival, while insulin receptor substrate (IRS) protein -1 and -2 and downstream PI-3 kinase→Akt→Foxo1 signaling cascade play key roles in many functions of insulin/IGF-1. Dysregulation of this branch of signaling cascades may provide a mechanism for insulin resistance as we observed in cells, animals, and even humans. Targeting this branch of IRS→Foxo1 signaling may provide us with fundamental strategies for drug development in the future.

摘要

胰岛素/胰岛素样生长因子-1信号传导在细胞代谢和存活的调控中起核心作用,而胰岛素受体底物(IRS)蛋白-1和-2以及下游的PI-3激酶→Akt→Foxo1信号级联在胰岛素/胰岛素样生长因子-1的许多功能中起关键作用。正如我们在细胞、动物甚至人类中所观察到的,这一信号级联分支的失调可能为胰岛素抵抗提供一种机制。针对IRS→Foxo1信号传导这一分支可能为我们未来的药物开发提供基本策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a37b/3763863/5c581e9ba281/nihms501753f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a37b/3763863/5c581e9ba281/nihms501753f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a37b/3763863/5c581e9ba281/nihms501753f1.jpg

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本文引用的文献

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Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2.胰岛素受体底物蛋白 IRS1 和 IRS2 的丝氨酸/苏氨酸磷酸化对胰岛素敏感性的调节。
Role of Peripheral and Central Insulin Resistance in Neuropsychiatric Disorders.
外周和中枢胰岛素抵抗在神经精神疾病中的作用。
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Role and mechanism of specialized pro-resolving mediators in obesity-associated insulin resistance.肥胖相关胰岛素抵抗中特异性促解决介质的作用及机制。
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Hepatic WDR23 proteostasis mediates insulin homeostasis by regulating insulin-degrading enzyme capacity.肝脏 WDR23 蛋白稳态通过调节胰岛素降解酶的能力来介导胰岛素稳态。
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Tea seed saponin‑reduced extract ameliorates palmitic acid‑induced insulin resistance in HepG2 cells.茶籽皂苷还原提取物改善棕榈酸诱导的 HepG2 细胞胰岛素抵抗。
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