Treatment with troglitazone increased insulin-stimulated IRS-1-associated PI 3-kinase activity and Akt activity in skeletal muscle biopsies from type 2 diabetic patients [26] and enhanced Akt phosphorylation in skeletal muscle from glucose-tolerant, insulin-resistant, first-degree relatives of type 2 diabetic patients [31]. Here, IRS1 is linked to type 2 diabetes mellitus.