Insulin-like growth factor-I receptor increases 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. In this study, aortic endothelial cells were cultured from diabetic BB rats. Their binding and internalization of insulin-like growth factor-I (IGF-I) were measured. IGF-I binding was higher in cells of diabetic rats than of control rats at both 37 degrees C (4.5% +/- 1.6% v 2.74% +/- 0.9% per mg protein, P < .05) and 4 degrees C (20.6% +/- 5.6% v 13.7% +/- 4.6% per mg protein, P < .01). Internalization of IGF-I also increased (1.62% +/- 0.2% v 0.74% +/- 0.15% of total count at 37 degrees C after 60 minutes, P < .05). Cross-linking studies showed that in cells from diabetic rats, the major band of 140 kd corresponding to the alpha-subunit of the IGF-I receptor increased in density by 50% compared with those from control rats. The IGF-I-stimulated tyrosine kinase activity (TKA) of partially purified receptor from cells of diabetic rats, measured using poly-glu-tyr as substrate, was normal. Since the biological effects of IGF-I are initiated by its binding to the IGF-I receptor, which is able to transduce mitogenic and metabolic signals, our results support the hypothesis that the IGF-I receptor is involved in the development of diabetic vascular complications.