Differential modulation of mitogenic and metabolic actions of insulin-like growth factor I in rat glomerular mesangial cells in high glucose culture.
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.
Kikkawa
R
R
Third Department of Medicine, Shiga University of Medical Science, Japan.
Haneda
M
M
Togawa
M
M
Koya
D
D
Kajiwara
N
N
Shigeta
Y
Y
D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology*; D007700:Kinetics; D008353:Mannitol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D000621:Aminoisobutyric Acids; D011994:Recombinant Proteins; C100049:2-aminoisobutyric acid; D008353:Mannitol; D007334:Insulin-Like Growth Factor I; D003847:Deoxyglucose; D005947:Glucose; D013936:Thymidine