Differential modulation of mitogenic and metabolic actions of insulin-like growth factor I in rat glomerular mesangial cells in high glucose culture

✍ Scribed by R. Kikkawa; M. Haneda; M. Togawa; D. Koya; N. Kajiwara; Y. Shigeta

• Publisher: Springer
• Year: 1993
• Tongue: English
• Weight: 660 KB
• Volume: 36
• Category: Article
• ISSN: 0012-186X
• DOI: 10.1007/bf00400228

✦ Synopsis

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 retool/l) of glucose (4.6 + 1.3 fold stimulation) was significantly suppressed as compared with that in the cells cultured in 11 mmol/1 glucose (17.5 + 0.8 fold). In contrast, [3H]-aminoisobutylic acid uptake into the mesangial cells was significantly enhanced by glucose (2.03 + 0.03 nmol~mg protein 1 15 min -L 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 sig-nificantly increased in the ceils 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-insulinlike growth factor I receptor level. These results may indicate that the differential modulation of the actions of insulin-like growth factor [ 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.