INS and type 2 diabetes mellitus: While Miyazaki et al. showed that the improvement in insulin-stimulated muscle glucose disposal after rosiglitazone therapy was associated with increased IRS-1 tyrosine phosphorylation and IRS-1-associated PI 3-kinase activity [32], Karlsson et al. found no changes in IRS-1/PI 3-kinase and Akt/AS160 signaling in patients with newly diagnosed type 2 diabetes, thus concluding that the insulin-sensitizing effects of rosiglitazone were independent of enhanced insulin signaling via these proteins [28].