IRS1 and Insulin resistance: IGFBP-3 levels are co-regulated by GH and insulin, allowing it to both stabilize IGF-1 and, via IGF-independent mechanisms—including inhibition of IRS-1/IR-β tyrosine phosphorylation, reduction of Akt phosphorylation and GLUT-4 translocation, and downregulation of adiponectin—to antagonize insulin signaling in peripheral tissues and promote insulin resistance (40).