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Mechanism of regulation of protein metabolism by insulin-like growth factor-I

胰岛素样生长因子-I调节蛋白质代谢的机制

基本信息

批准号：
08456063
负责人：
NOGUCHI Tadashi
金额：
$ 4.93万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

Insulin-like growth factor-I (IGF-I) is a hormone the structure and function of which are similar to those of insulin. However, as we and others have proved, its physiological role is presumed to be different from that of insulin. IGF-I circulates in blood complexed with the specific binding proteins which are referred to as IGF-binding proteins (IGFBPs). Seven IGFBPs have been identified. IGFBPs have been presumed to regulate the activity of IGF-I and IGF-II.In order to elucidate the role of IGF-I and IGFBPs in the regulation of protein metabolism, we investigated the concentration of IGF-I and IGFBP-1 in the rats fed on a protein-free diet, given streptozotocin or dexamethasone.Plasma IGF-I concentration correlated with RNA/protein ratio in skeletal muscle except in the case of dexamethasone treatment. RNA/protein ratio has been shown to be an index of the activity of protein synthesis in tissues. Therefore, the results mean that IGF-I is an important factor which regulates muscle protein synthesis.On the contrary, plasma IGFBP-1 concentration inverseiy correlated with the RNA/protein ratio in skeletal muscle. There was no exception in this case. these observations suggest that IGFBP-1 plays an important role directly regulating the activity of IGF-I and muscle protein synthesis.We conclude that IGF-I regulates muscle protein synthesis and IGFBP-1 regulates the activity of IGF-I,thereby determining the activity of protein synthesis in skeletal muscle.

胰岛素样生长因子- i （IGF-I）是一种结构和功能与胰岛素相似的激素。然而，正如我们和其他人已经证明的那样，它的生理作用被认为与胰岛素不同。igf - 1与特异性结合蛋白（igf结合蛋白，igfbp）结合在血液中循环。已经确定了7个igfbp。igfbp被认为可以调节IGF-I和IGF-II的活性。为了阐明IGF-I和igfbp在调节蛋白质代谢中的作用，我们研究了饲喂无蛋白饮食、给予链脲佐菌素或地塞米松的大鼠中IGF-I和IGFBP-1的浓度。除地塞米松治疗外，血浆igf - 1浓度与骨骼肌RNA/蛋白比值相关。RNA/蛋白质比率已被证明是组织中蛋白质合成活性的一个指标。因此，这意味着igf - 1是调节肌肉蛋白合成的重要因子。相反，血浆IGFBP-1浓度与骨骼肌RNA/蛋白比呈负相关。这件事没有例外。这些观察结果表明，IGFBP-1在直接调节igf -1活性和肌肉蛋白合成方面起着重要作用。我们得出结论，IGF-I调节肌肉蛋白质合成，IGFBP-1调节IGF-I的活性，从而决定骨骼肌蛋白质合成的活性。