Effects of Metformin and Rosiglitazone Treatment on Insulin Signaling and Glucose Uptake in Patients With Newly Diagnosed Type 2 Diabetes A Randomized Controlled Study

The effect of metformin or rosiglitazone monotherapy versus placebo on insulin signaling and gene expression in skeletal muscle of patients with newly diagnosed type 2 diabetes was determined. A euglycemic-hyperinsuline-mic clamp, combined with skeletal muscle biopsies and glucose uptake measurements over rested and exer-cised muscle, was performed before and after 26 weeks of metformin (n 9), rosiglitazone (n 10), or placebo (n 11) treatment. Insulin-mediated whole-body and leg muscle glucose uptake was enhanced 36 and 32%, respectively, after rosiglitazone (P< 0.01) but not after metformin or placebo treatment. Insulin increased in-sulin receptor substrate 1 (IRS-1) tyrosine phosphor-ylation, IRS-1–associated phosphatidylinositol (PI) 3-kinase activity, and phosphorylation of Akt Ser473 an