Summary
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]-aminoisobutylic 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.
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Kikkawa, R., Haneda, M., Togawa, M. et al. Differential modulation of mitogenic and metabolic actions of insulin-like growth factor I in rat glomerular mesangial cells in high glucose culture. Diabetologia 36, 276–281 (1993). https://doi.org/10.1007/BF00400228
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DOI: https://doi.org/10.1007/BF00400228