[Metabolic and mitogenic effects of insulin-like growth factor I on rat glomerular mesangial cells cultured under high concentration of glucose].
Recent studies indicate the important roles of mesangial cell dysfunction and insulin-like growth factor I (IGF-I) in the development of diabetic nephropathy. In order to know whether hyperglycemia could alter IGF-I action on mesangial cells, we examined mitogenic and metabolic effects of IGF-I on mesangial cells. Mesangial cells revealed to express considerable numbers of receptors specific to IGF-I will relatively small numbers of insulin receptors. The uptake of [3H]-2-deoxy-glucose, [3H]-aminoisobutyric acid (AIB), or [3H]-thymidine into mesangial cells was stimulated by IGF-I at physiological concentrations. Under high concentrations of glucose (55 mM), the stimulation of thymidine uptake by IGF-I was significantly suppressed from 5863 +/- 549 (at 11 mM glucose) to 1731 +/- 146 DPM/100 micrograms/prot. On the contrary, AIB incorporation by IGF-I was significantly enhanced in the cells cultured under high concentration of glucose, as 2.03 +/- 0.03n mol/mg protein/15 min at 55 mM glucose vs 0.59 +/- 0.01 at 11 mM glucose. In conclusion; 1) IGF-I had metabolic and mitogenic effects on rat mesangial cells at physiological concentrations. 2) under excess glucose conditions, mitogenic action of IGF-I on rat mesangial cells was suppressed, while amino acid incorporation was enhanced. These results suggest that modulation of IGF-I effects on mesangial cell by glucose could be associated with mesangial cell dysfunction in diabetes.
Togawa
M
M
Third Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
Kikkawa
R
R
Haneda
M
M
Shigeta
Y
Y
D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D003847:Deoxyglucose / Q000493:pharmacokinetics; D003928:Diabetic Nephropathies / Q000209:etiology; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008938:Mitosis; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine
D000621:Aminoisobutyric Acids; D003470:Culture Media; D007334:Insulin-Like Growth Factor I; D003847:Deoxyglucose; D013936:Thymidine