Previous work on insulin regulation of gene activity revealed that insulin-resistance alters insulin regulated gene expression. Insulin- resistance alters immediate early gene expression in a gene specific manner, suggesting multiple insulin signal pathways that result in changes in gene expression. Two genes, c-Ha-ras and myf5, displayed the same types of insulin mediated responses in insulin-sensitive and -resistant individuals suggesting the same mode of regulation. To isolate the cis- acting sequences and the trans-acting factors that bind these sequences that are responsible for the changes in RNA levels for these two genes, genomic clones of myf5 have been isolated. The 5' regulatory region will be analyzed for insulin responsive elements. Once isolated the insulin responsive DNA element can be utilized to test insulin-sensitive and - resistant skeletal muscle for differences in the trans-acting factor that interacts with this element.
