Kikkawa R, Haneda M, Togawa M, Koya D, Kajiwara N, Shigeta Y
Third Department of Medicine, Shiga University of Medical Science, Japan.
Diabetologia. 1993 Apr;36(4):276-81. doi: 10.1007/BF00400228.
In order to explore the possible contribution of insulin-like growth factor I to the development of diabetic nephropathy, the effect of glucose on the mitogenic and metabolic actions of insulin-like growth factor I in cultured rat glomerular mesangial cells was examined. The stimulation of [3H]-thymidine incorporation by insulin-like growth factor I in the cells exposed to high concentrations (55 mmol/l) of glucose (4.6 +/- 1.3 fold stimulation) was significantly suppressed as compared with that in the cells cultured in 11 mmol/l glucose (17.5 +/- 0.8 fold). In contrast, [3H]-amino-isobutylic acid uptake into the mesangial cells was significantly enhanced by glucose (2.03 +/- 0.03 nmol.mg protein-1. 15 min-1 at 55 mmol/l glucose vs 0.59 +/- 0.01 at 11 mmol/l glucose), while 2-deoxyglucose uptake remained unchanged. [125I]-insulin-like growth factor I binding was slightly but significantly increased in the cells exposed to high concentrations of glucose. Thus, glucose may modulate the mitogenic and metabolic actions of insulin-like growth factor I differently in cultured mesangial cells probably at the post-insulin-like growth factor I receptor level. These results may indicate that the differential modulation of the actions of insulin-like growth factor I by glucose could result in the increase in amino acid uptake and decrease in the cell proliferation in the mesangial cells, possibly leading to enhanced mesangial matrix synthesis with a relatively small increase in mesangial cell volume as seen in diabetic nephropathy.
为了探讨胰岛素样生长因子I对糖尿病肾病发展的可能作用，研究了葡萄糖对培养的大鼠肾小球系膜细胞中胰岛素样生长因子I的促有丝分裂和代谢作用的影响。与在11 mmol/l葡萄糖中培养的细胞相比，在高浓度（55 mmol/l）葡萄糖中培养的细胞中，胰岛素样生长因子I对[3H] - 胸腺嘧啶核苷掺入的刺激作用（4.6±1.3倍刺激）显著受到抑制（在11 mmol/l葡萄糖中为17.5±0.8倍）。相反，葡萄糖显著增强了系膜细胞对[3H] - 氨基异丁酸的摄取（55 mmol/l葡萄糖时为2.03±0.03 nmol·mg蛋白-1·15 min-1，11 mmol/l葡萄糖时为0.59±0.01），而2 - 脱氧葡萄糖的摄取保持不变。在暴露于高浓度葡萄糖的细胞中，[125I] - 胰岛素样生长因子I结合略有但显著增加。因此，葡萄糖可能在培养的系膜细胞中，可能在胰岛素样生长因子I受体后水平上，以不同方式调节胰岛素样生长因子I的促有丝分裂和代谢作用。这些结果可能表明，葡萄糖对胰岛素样生长因子I作用的差异调节可能导致系膜细胞中氨基酸摄取增加和细胞增殖减少，这可能导致系膜基质合成增加，而系膜细胞体积增加相对较小，如在糖尿病肾病中所见。
