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pathophysiological significance of insulin-like growth factor binding protein

胰岛素样生长因子结合蛋白的病理生理意义

基本信息

批准号：
03671168
负责人：
TAKANO Kazue
金额：
$ 1.34万
依托单位：
Tokyo Women's Medical Collage
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

Insulin-like growth factor(IGF)in serum and tissue binds to specific binding proteins. We investigated serum IGF binding proteins(IGFBPs)in various conditions using Western ligand blotting., Western immunoblotting of IGFBP-3 and RIA of IGFBP-1.Serum from normal subjects revealed four IGFBPs with mol wts of 41/38, 34, 30, 24KD identified as IGFBP-3, 2, 1, 4 using Western ligand blotting. Serum IGFBP-3 decreased in the patients with GH deficiency and increased in acromegalic patients. IGFBP-3 sightly increased in patients with hypothyroidism and IGFBP-3 decreased and IGFBP-2 increased in malnutrition. All IGFBPs decreased in patients with severe liver dysfunction. These data show that serum IGFBP-3 was produced from liver and depends on GH and nutritional state. In patients with nonislet cell tumor associated with hypoglycemia(NICTH), serum IGFBP-2 increased. In two patients with NICTH IGFBP-2 decreased and IGFBP-3 increased after successful tumor resection.Serum IGFBP-3 was also studied using Western immunoblotting. Serum from normal subjects revealed three bands of IGFBP-3 with mol wts of 41, 38, 30KD. These three bands of IGFBP-3 increased in acromegalic patients and decreased in patients with GH deficiency. Serum in pregnant wemen shows a large amount of 30KD IGFBP-3. In some patients with NICTH most of all IGFBP-3 was 30KD and this band disappeared after successful tumor resection.When 0.06mg/kg or 0.12mg/kg IGF-I was administered to 5 normal subjects, IGFBP-1, which was measured using RIA, increased at 1h and reached the peak at 5hs.We reported serum IGFBP in various conditions. These observations are useful for studying IGF bioavailability.

血清和组织中的胰岛素样生长因子(IGF)与特定的结合蛋白结合。本文用免疫印迹法、免疫印迹法和放射免疫法检测了不同条件下血清中胰岛素样生长因子结合蛋白(IGFBP-3)和IGFBP-1的含量。GH缺乏症患者血清IGFBP-3降低，肢端肥大症患者血清IGFBP-3升高。甲状腺功能减退组IGFBP-3明显升高，营养不良组IGFBP-3降低，IGFBP-2升高。在严重肝功能不全的患者中，所有IGFBP均降低。这些数据表明，血清IGFBP-3是由肝脏产生的，并与生长激素和营养状态有关。非胰岛细胞肿瘤合并低血糖(NICTh)患者血清IGFBP-2升高。在2例NICTH患者中，成功切除肿瘤后IGFBP-2降低，IGFBP-3升高。同时用免疫印迹法检测血清IGFBP-3。正常人血清中有三条IGFBP-3条带，其分子质量分别为41、38、30KD。这三条带在肢端肥大症患者中升高，在生长激素缺乏症患者中降低。妊娠妇女血清中有大量的30KD IGFBP-3。在一些NICTH患者中，IGFBP-3大部分为30KD，在肿瘤成功切除后该条带消失。5名正常人分别给予0.06 mg/kg和0.12 mg/kg的IGF-I，用放射免疫法测定IGFBP-1，1h开始升高，5h达到峰值。这些观察结果对研究胰岛素样生长因子的生物利用度很有用。