Changes of insulin receptor in aortic endothelial cells from diabetic rats.
Endothelial cells are likely to play an important role in the development of diabetic vascular diseases since they are exposed directly to the abnormal circulating metabolites of diabetes and may be easily damaged early in the natural course of vascular complications. Recently, we have demonstrated a decrease of insulin binding and autophosphorylation of the insulin receptor in cultured capillary endothelial cells of diabetic rats. In this study, similar defects in insulin receptor of aortic endothelial cells cultured from diabetic BB rats were found. The specific insulin binding was 45% lower in cells from diabetic than from non-diabetic rats (3.9 +/- 1.3 vs 7.3 +/- 1.2% per mg protein, p less than 0.05), which was due to a decrease of cell surface binding sites. In contrast to the decrease in insulin binding, insulin-like growth factor-I binding was higher in cells of diabetic than control rats (20.6 +/- 5.6 vs 13.7 +/- 4.6% per mg protein). The decrease in insulin binding could not be induced by the two-week treatment of endothelial cells from non-diabetic rats with medium containing high concentration of glucose (400 mg/dl). Insulin-induced tyrosine kinase activity of partially purified insulin receptor measured using poly-glutyr as substrate was also lower in cells from diabetic rats (normal:1.4 +/- 0.6-fold; diabetic 0.5 +/- 0.3-fold above baseline; (p less than 0.05). These data suggest that the diabetic milieu in vivo can induce persistent defects in insulin receptor of aortic endothelial cells. Further studies are warranted to understand the potential pathophysiological role of these defects.
Kwok
C F
CF
Department of Medicine, Veterans General Hospital-Taipei, ROC.
Jap
T S
TS
Ho
L T
LT
D000818:Animals; D001011:Aorta; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007700:Kinetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011913:Rats, Inbred BB; D011972:Receptor, Insulin / Q000378:metabolism*; D012016:Reference Values
D007328:Insulin; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin