Characterization of the Receptors for Insulin and the Insulin-Like Growth Factors on Micro- and Macrovascular Tissues*

Publisher Website
Google Scholar
Abstract
Insulin and insulin-like growth factors (IGF) have been implicated in the pathogenesis of diabetic retinopathy and peripheral vascular complications. Retinal capillary endothelial cells respond to insulin and IGF for metabolic and growth effects, whereas aortic endothelial cells are not responsive. In contrast, vascular supporting cells from both retinal capillaries (i.e., pericytes) and aorta (i.e., smooth muscle cells) responded equally to insulin, IGF-I, and IGF-II. The structure and ligand specificities of the receptor for these peptides were studied by covalently cross-linking 125I-labeled peptide hormones to their respective receptors using disuccinimidyl suberate, followed by polyacrylamide gel electrophoresis and autoradiography. The binding subunit of the insulin receptor, .alpha.-subunit, for all cell types was found to have a MW 145,000 under reduced conditions. Labeling of this band was inhibited by 10-9 M insulin, antiinsulin receptor antibodies, and 10-8 M IGF-I, but not by multiplication-stimulating activity (IGF-II). The .beta.-subunit of the insulin receptor in endothelial cells was identified by its ability to be autophosphorylated when stimulated by insulin and was found to have a MW of 99,000. Covalent cross-linking of IGF-I to its receptor revealed MW of 145,000, similar to that of insulin receptor, except that IGF-I was 100-fold more potent than insulin in competing with [125I]IGF-I for binding. [125I]IGF-II in all cells was cross-linked to receptor with MW of 260,000 and 230,000 under reduced and nonreduced conditions, respectively. IGF-I competed weakly with [125I]IGF-II, whereas insulin was ineffective. [125I]IGF-II also bound to the band with .alpha. MW of 135,000, which was inhibited by insulin, IGF-I, and IGF-II. Receptors for insulin, IGF-I, and IGF-II on cells from micro- and macrovessels are biochemically similar to those in other cells. The finding of large numbers of IGF-I and IGF-II receptors on endothelial cells suggests that these growth factors play a physiological role and are involved in vascular complications associated with diabetes.