Insulin and insulin-like growth factor receptors have been recently identified in vascular tissues, including retinal and cerebral microvessels, isolated renal glomeruli, and cultured endothelial cells from micro and macrovascular tissues. In disease states, such as diabetes mellitus and atherosclerosis, there is an apparent alteration in vascular basement membrane synthesis, smooth muscle endothelial cell proliferation. In the proposed study, the specific aims are to: (1) Compare insulin, IGF-I and IGF-II receptors in microvascular and macrovascular preparations solubilized with Triton X-100. (2) Determine whether insulin, IGF-I and IGF-II are taken up by blood vessels and/or transported out of surrounding tissues, using rat testes as an example of a blood-tissue barrier. (3) Determine whether insulin, IGF-I and IGF-II play a physiological role in vascular tissues by examining tyrosine protein kinase activity, 14C-D-glucose incorporation into lipids, and 35S-sulfate incorporation into basement membrane components. Recently, rodent testes have been shown to contain high levels of IGF-I and we have shown that purified Leydig cell have specific insulin, IGF-I, and IGF-II receptors. In primary cultures, IGFs and insulin stimulate basal and hCG-stimulated steroidogenesis. IGF receptors in placenta and vascular tissues have been implicated as a means of transporting serum IGFs into tissue compartments. In the proposed study, insulin and growth factor interaction with vascular tissue will be examined in order to determine whether these peptides play an important role in blood vessel function.
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