Experimental Diabetes Increases Insulinlike Growth Factor I and II Receptor Concentration and Gene Expression in Kidney
Experimental Diabetes Increases Insulinlike Growth Factor I and II Receptor Concentration and Gene Expression in Kidney
复制标题
实验性糖尿病增加肾脏中胰岛素样生长因子 I 和 II 受体的浓度和基因表达
作者：
H. Werner;Z. Shen‐Orr;B. Stannard;B. Burguera;C. Roberts;D. Leroith
胰岛素样生长因子I（IGF-I）是一种促有丝分裂激素，在生长发育中具有重要的调节作用。IGF-I作用的靶器官之一是肾脏，其合成丰富的IGF-I受体和IGF-I本身。为了研究IGF-I和IGF-I受体在糖尿病的主要并发症之一肾病的发展中的参与，我们测量了这些基因在链脲佐菌素诱导的糖尿病大鼠的肾脏和其他组织中的表达。在相同的组织中测量125 I标记的IGF-I与粗膜的结合。我们观察到糖尿病肾脏IGF-I受体mRNA的稳态水平增加了2.5倍，伴随着IGF-I结合增加了2.3倍。除了IGF-I与IGF-I受体结合的增加外，还与可能代表IGF结合蛋白的低分子量物质结合。IGF-I-肽mRNA水平无变化。类似地，IGF-II受体mRNA水平和IGF-II结合在糖尿病肾脏中显著增加。胰岛素治疗后，IGF-I和IGF-II受体mRNA水平以及IGF-I和IGF-II结合恢复至对照值。由于IGF-I受体能够在其酪氨酸激酶结构域活化时抑制促有丝分裂信号，我们推测，在其他因素中，糖尿病肾脏中高水平的受体也可能参与糖尿病肾病的发展。IGF-II受体在糖尿病肾脏中的表达增加可能对溶酶体酶的细胞内转运和包装很重要，尽管不能排除该受体在信号转导中的作用。最后，IGF结合蛋白的可能作用需要进一步研究。
Insulinlike growth factor I (IGF-I) is a mitogenic hormone with important regulatory roles in growth and development. One of the target organs for IGF-I action is the kidney, which synthesizes abundant IGF-I receptors and IGF-I itself. To study the involvement of IGF-I and the IGF-I receptor in the development of nephropathy, one of the major complications of diabetes mellitus, we measured the expression of these genes in the kidney and in other tissues of the streptozocin-induced diabetic rat. The binding of 125I-labeled IGF-I to crude membranes was measured in the same tissues. We observed a 2.5-fold increase in the steady-state level of IGF-I–receptor mRNA in the diabetic kidney, which was accompanied by a 2.3-fold increase in IGF-I binding. In addition to this increase in IGF-I binding to the IGF-I receptor, there was also binding to a lower-molecular-weight material that may represent an IGF-binding protein. No change was detected in the level of IGF-I–peptide mRNA. Similarly, IGF-II–receptor mRNA levels and IGF-II binding were significantly increased in the diabetic kidney. IGF-I– and IGF-II-receptor mRNA levels and IGF-I and IGF-II binding returned to control values after insulin treatment. Because the IGF-I receptor is able to transduce mitogenic signals on activation of its tyrosine kinase domain, we hypothesize that, among other factors, high levels of receptor in the diabetic kidney may also be involved in the development of diabetic nephropathy. Increased IGF-II–receptor expression in the diabetic kidney may be important for the intracellular transport and packaging of lysosomal enzymes, although a role for this receptor in signal transduction cannot be excluded. Finally, the possible role of IGF-binding proteins requires further study.
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DOI：
10.1073/pnas.87.1.404
发表时间：
1990-01-01
影响因子：
11.1
作者：
ROY, S;SALA, R;LORENZI, M
通讯作者：
LORENZI, M
II 型胰岛素样生长因子受体不介导人成纤维细胞中的脱氧核糖核酸合成。
DOI：
10.1210/jcem-64-6-1142
发表时间：
1987
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Furlanetto,RW;DiCarlo,JN;Wisehart,C
通讯作者：
Wisehart,C
肾肥大期间胰岛素样生长因子 I 表达的双重调节。
DOI：
10.1152/ajprenal.1989.257.2.f252
发表时间：
1989
期刊：
The American journal of physiology
影响因子：
--
作者：
Lajara,R;Rotwein,P;Bortz,JD;Hansen,VA;Sadow,JL;Betts,CR;Rogers,SA;Hammerman,MR
通讯作者：
Hammerman,MR
II 型胰岛素样生长因子受体不介导 H-35 肝癌细胞中 DNA 合成的增加。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Mottola,C;Czech,MP
通讯作者：
Czech,MP
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
发表时间：
1988
期刊：
The American journal of physiology
影响因子：
--
作者：
Arnqvist,HJ;Ballermann,BJ;King,GL
通讯作者：
King,GL