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首页> 外文期刊>Molecular and Cellular Biology >Essential Role of Insulin and Insulin-Like Growth Factor 1 Receptor Signaling in Cardiac Development and Function
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Essential Role of Insulin and Insulin-Like Growth Factor 1 Receptor Signaling in Cardiac Development and Function

机译：胰岛素和胰岛素样生长因子1受体信号传导在心脏发育和功能中的基本作用

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Cardiovascular disease is the leading cause of death in people with type 2 diabetes and is linked to insulin resistance even in the absence of diabetes. Here we show that mice with combined deficiency of the insulin receptor and insulin-like growth factor 1 (IGF-1) receptor in cardiac and skeletal muscle develop early-onset dilated cardiomyopathy and die from heart failure within the first month of life despite having a normal glucose homeostasis. Mice lacking the insulin receptor show impaired cardiac performance at 6 months, and mice lacking the insulin receptor plus one Igf1r allele have slightly increased mortality. By contrast, mice lacking the IGF-1 receptor or the IGF-1 receptor plus one Ir allele appear normal. Morphological characterization and oligonucleotide array analysis of gene expression demonstrate that prior to development of these physiological defects, mice with combined deficiency of both insulin and IGF-1 receptors have a coordinated down-regulation of genes encoding components of the electron transport chain and mitochondrial fatty acid beta-oxidation pathways and altered expression of contractile proteins. Thus, while neither the insulin receptor nor IGF-1 receptor in muscle is critical for glucose homeostasis during the first month of life, signaling from these receptors, particularly the insulin receptor, is required for normal cardiac metabolism and function.
机译：心血管疾病是2型糖尿病患者的主要死亡原因，即使没有糖尿病也与胰岛素抵抗相关。在这里，我们显示了在心肌和骨骼肌中胰岛素受体和胰岛素样生长因子1（IGF-1）受体联合缺乏的小鼠发展为早期发作的扩张型心肌病，尽管在生命的第一个月内因心力衰竭而死亡。正常的葡萄糖稳态。缺乏胰岛素受体的小鼠在6个月时心脏功能受损，而缺乏胰岛素受体和1个 Igf1r 等位基因的小鼠的死亡率则略有增加。相比之下，缺乏IGF-1受体或IGF-1受体加一个 Ir 等位基因的小鼠表现正常。基因表达的形态学表征和寡核苷酸阵列分析表明，在出现这些生理缺陷之前，胰岛素和IGF-1受体联合缺乏的小鼠具有协调的编码电子转运链和线粒体脂肪酸成分的基因下调β氧化途径和收缩蛋白表达的改变。因此，尽管在生命的第一个月中，肌肉中的胰岛素受体和IGF-1受体都不是葡萄糖稳态的关键，但正常的心脏代谢和功能需要这些受体的信号传递，尤其是胰岛素受体。

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