Low cellular IRS 1 gene and protein expression predict insulin resistance and NIDDM.Impairment of insulin-induced glucose uptake by skeletal muscles from high-salt-fed Dahl S rats was neither due to changes in the insulin receptor number, mRNA or binding affinity, nor due to diminished expression of GLUT4 protein. Impairment in the insulin signaling pathway might possibly be downstream of the insulin receptor and upstream of GLUT4, possibly in the IRS-1 and/or IRS-2 signaling molecules. This evidence concerns the gene IRS1 and type 2 diabetes mellitus.