Mechanisms of Modulation of IGF's Action

IGF 作用的调节机制

• 批准号: 08044193
• 负责人: TAKAHASHI Shin-Ichiro
• 金额: $ 8.45万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08044193/
• 关键词: IGS-1; IGFBP; IGF receptor; tropic hormone; cAMP; tyrosine kinase; cell growth cell differentiation; 細胞分化; IGF-1; IGF-1レセプター; IRS; 情報伝達; IGF-BP; ICFBP; ICF-1レセプタ

Recent evidence, derived from studies using knock-out or overexpression mice, indicates that insulinlike growth factors (IGFs) and/or their receptors are essential for the normal development and growth of mammals. Further, in many cell types IGFs have been shown to possess a variety of bioactivities, including the ability to induce cell proliferation and differentiaton, to inhibit cell apoptosis, and to maintain cell functio. IGFs circulates in the plasma and throughout the extracellular space as a complex with several specific binding proteins (IGFBPs). IGFBPs are believed at present to control half-lives of IGFs and modulate IGFs availability ; however, their physiological roles are still unclear. Despite the profuseness and diversity of IGFs bioactivities, the in vitro biological effects of IGFs are relatively weak and often are not demonstrable except in the presence of other hormones or growth factors. From this background, this study was undertaken to determine extracellular and … More intracellular mechanisms to modulate IGFs bioactivities in response to other hormones or growth factors, and different physiological conditions. Firstly, under various physiological conditions, we analyzed production of IGFs and IGFBPs interaction between IGFs and IGFBPs in serum, expression of IGF receptors. Our results suggested that expression of IGF/IGFBP/IGF receptors is regulated in different manners, resulting in reasonable IGFs bioactivities in response to each physiological situation. In additions, in endocrine cells, we demonstrated that tropic hormones prime cells to respond to IGF-I through cross-talk mechanisms of the intracellular signals. In liver cells, the similar potentiation between insulin and camp was observed, suggesting that the cross-talk mechanisms are very important to control insulin-like activities in general. From a series of these data, we concluded that IGF bioactivities are modulated by the process of 1) IGFs production, 2) IGFBPs production, 3) interaction between IGFs and IGFBPs, 4) IGF receptor expression, and 5) IGF signal transduction, in response to other hormones or growth factors as well as physiological conditions. This modulation must be required for normal development and growth of mammals. Less

最近的证据，来自使用基因敲除或过表达小鼠的研究，表明胰岛素样生长因子（IGFs）和/或其受体是哺乳动物的正常发育和生长所必需的。此外，在许多细胞类型中，IGFs已显示具有多种生物活性，包括诱导细胞增殖和分化、抑制细胞凋亡和维持细胞功能的能力。IGFs在血浆中循环，并作为与几种特异性结合蛋白（IGFBPs）的复合物在整个细胞外空间循环。目前认为IGFBPs可以控制IGF的半衰期并调节IGF的可用性;然而，它们的生理作用仍不清楚。尽管IGFs的生物活性丰富多样，但IGFs的体外生物学效应相对较弱，并且通常无法证明，除非存在其他激素或生长因子。在此背景下，进行本研究以确定细胞外和 ...更多信息 调节IGFs生物活性的细胞内机制，以响应其他激素或生长因子和不同的生理条件。首先，在不同生理条件下，我们分析了IGFs和IGFBPs的产生，血清中IGFs和IGFBPs之间的相互作用，IGF受体的表达。我们的研究结果表明，IGF/IGFBP/IGF受体的表达以不同的方式进行调节，从而产生合理的IGFs生物活性，以响应每种生理情况。此外，在内分泌细胞中，我们证明了营养激素通过细胞内信号的串扰机制引发细胞对IGF-I的反应。在肝细胞中，观察到胰岛素和cAMP之间的类似增强作用，这表明串扰机制对于一般控制胰岛素样活性非常重要。从一系列这些数据中，我们得出结论，IGF生物活性是由以下过程调节的：1）IGF产生，2）IGFBPs产生，3）IGF和IGFBPs之间的相互作用，4）IGF受体表达，和5）IGF信号转导，响应于其他激素或生长因子以及生理条件。这种调节必须是哺乳动物正常发育和生长所必需的。少

项目成果

Higashi Y et al.: "Effect of proteins restriction on the messenger ribonucleic acids contents of bone matrix proteins, insulin-like growth factors and insulin-like growth factor binding proteins in femur of ovarieetomized rats." Brit.J.Nutr.75. 811-823 (1

Higashi Y 等人：“蛋白质限制对去卵巢大鼠股骨中骨基质蛋白、胰岛素样生长因子和胰岛素样生长因子结合蛋白的信使核糖核酸含量的影响。”

Higashi Y et al.: "Effect of protein restriction on the messenger ribonucleic acid contents of insulin-like growth factor-I and insulin-like growth factor binding proteins in liver of ovariectomized rats." Brit.J.Nutr.79. 447-453 (1998)

Higashi Y 等人：“蛋白质限制对卵巢切除大鼠肝脏中胰岛素样生长因子-I 和胰岛素样生长因子结合蛋白的信使核糖核酸含量的影响。”

Miyatake N et al.: "Differential distribution of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding proteins (IGFBPs) in experimental diabetic rat kidney." Nephron. in press.

Miyatake N 等人：“实验性糖尿病大鼠肾脏中胰岛素样生长因子-1 (IGF-1) 和胰岛素样生长因子结合蛋白 (IGFBP) 的差异分布。”

Takahashi S-I: "Mini-review : What are insulin-like growth factors? (Japanese)" Nippon Nougei Kagaku Kaishi. 72. 159-160 (1998)

高桥 S-I：“迷你评论：什么是胰岛素样生长因子？（日语）”Nippon Nougei Kagaku Kaishi。

Takahashi S-I: "Mini-review : Regulation of insulin-like growth factors' activities (Japanese)" Nippon Nougei Kagaku Kaishi. 72. 161-166 (1998)

Takahashi S-I：“迷你评论：胰岛素样生长因子活性的调节（日语）”Nippon Nougei Kagaku Kaishi。