Receptors for and effects of insulin and IGF-I in rat glomerular mesangial cells.

Receptors for and effects of insulin and IGF-I in rat glomerular mesangial cells.
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大鼠肾小球系膜细胞中胰岛素和 IGF-I 的受体及其作用。

DOI:
10.1152/ajpcell.1988.254.3.c411
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发表时间:
1988
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
King,GL
King,GL
中科院分区:
--
文献类型:
--
作者:
Arnqvist,HJ;Ballermann,BJ;King,GL

文献摘要

被引文献

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在培养的大鼠肾系膜细胞中研究了胰岛素和胰岛素样生长因子I (IGF-I)的受体及其生物学效应。125I-IGF的特异性结合(5.8%/0.2 mg细胞蛋白)比125i -胰岛素的特异性结合(0.2%/2 mg细胞蛋白)高200倍以上。8 × 10(-9) M未标记的胰岛素可抑制50%的125i -胰岛素结合。对于125I-IGF-I, 50%的抑制需要1.8 x 10(-9) M未标记的IGF-I。125I-IGF-I也被IGF-II和胰岛素取代,但其效力分别比IGF-I低10倍和100倍。使用二琥珀酰亚基(DSS)将125i -胰岛素和125I-IGF-I与其受体交联,并使用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和放射自显影技术对受体进行鉴定,发现一条分子质量为135 kDa的条带,可能与胰岛素受体的α亚基相对应,而一条分子质量为145 kDa的主条带则与胰岛素受体的α亚基相对应。胰岛素和igf - 1都刺激了[3H]胸腺嘧啶与DNA的结合。胰岛素在1.6 × 10(-8) M, IGF-I在1.2 × 10(-9) M时达到半最大效应。对DNA合成无加性影响。8 × 10(-10) M的胰岛素增加了系膜细胞中[14C]葡萄糖的积累,而igf -1的效力则降低了10倍。
Receptors for and biological effects of insulin and insulin-like growth factor I (IGF-I) were studied in cultured rat renal mesangial cells. Specific binding of 125I-IGF was over 200-fold greater (5.8%/0.2 mg cell protein) than the specific binding of 125I-insulin (0.2%/2 mg cell protein). Fifty percent inhibition of 125I-insulin binding was obtained with 8 x 10(-9) M unlabeled insulin. For 125I-IGF-I, 50% inhibition required 1.8 x 10(-9) M unlabeled IGF-I. 125I-IGF-I was also displaced by IGF-II and insulin but at 10-and 100-fold lower potencies, respectively, than IGF-I. Cross-linking of 125I-insulin and 125I-IGF-I to their receptors, using disuccinimidyl suberate (DSS), and identification of the receptor with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography showed a band with a molecular mass of 135 kDa, probably corresponding to the alpha-subunit of the insulin receptor and a major band with a molecular mass of 145 kDa for the alpha-subunit of the IGF-I receptor. Both insulin and IGF-I stimulated the incorporation of [3H]thymidine into DNA. A half-maximal effect was obtained at 1.6 x 10(-8) M for insulin and 1.2 x 10(-9) M for IGF-I. No additive effect on DNA synthesis was observed. Insulin at 8 x 10(-10) M increased the accumulation of [14C]glucose in mesangial cells, whereas IGF-I was 10-fold less potent.