Tissue-specificity of insulin action and resistance
Tissue-specificity of insulin action and resistance
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DOI：
10.3109/13813455.2011.563748
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发表时间：
2011-07-01
影响因子：
3
通讯作者：
Benito, Manuel
中科院分区：
文献类型：
--
作者：
Benito, Manuel
胰岛素抵抗是许多糖尿病前期状态最重要的病理生理特征。2型糖尿病是一种复杂的代谢性疾病，其发病机制涉及外周胰岛素作用和胰岛β细胞分泌胰岛素的异常。以组织特异性的方式建立单基因或多基因基因操纵的小鼠模型，有助于阐明胰岛素作用的组织特异性及其在整体胰岛素抵抗中的作用。然而，要完全理解胰岛素作用和抵抗的分子基础，就需要识别调节胰岛素刺激的增殖、分化和代谢的细胞内途径。相应地，从缺乏胰岛素受体或敏感候选基因如IRS-1、IRS-2、IRS-3、IR和PTP1B的棕色脂肪组织、肝脏和胰岛等来源的胰岛素靶组织来源的细胞系被开发出来。事实上，这些细胞系对于理解胰岛素作用和不作用的组织特异性也非常有用。
Insulin resistance is the most important pathophysiological feature in many pre-diabetic states. Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion by pancreatic beta cells. The creation of monogenic or polygenic genetically manipulated mice models in a tissue-specific manner was of great help to elucidate the tissue-specificity of insulin action and its contribution to the overall insulin resistance. However, complete understanding of the molecular bases of the insulin action and resistance requires the identification of the intracellular pathways that regulate insulin-stimulated proliferation, differentiation and metabolism. Accordingly, cell lines derived from insulin target tissues such as brown adipose tissue, liver and beta islets lacking insulin receptors or sensitive candidate genes such as IRS-1, IRS-2, IRS-3, IR and PTP1B were developed. Indeed, these cell lines have been also very useful to understand the tissue-specificity of insulin action and inaction.