IRS1 and chronic kidney disease: However, there is resistance to post-receptor signal transduction; both auto-phosphorylation of the IGF-1R tyrosine kinase and activity of the IGF-1R tyrosine kinase to the exogenous insulin receptor substrate-1 (IRS-1), a natural substrate for IGF-1 receptor tyrosine kinase, are diminished in skeletal muscle of CKD rats.