TROGLITAZONE ENHANCES GLUCOSE-UPTAKE AND INHIBITS MITOGEN-ACTIVATED PROTEIN-KINASE IN HUMAN AORTIC SMOOTH-MUSCLE CELLS

The thiazolidinedione analogue troglitazone is an antidiabetic agent t hat improves insulin resistance in rodents and humans. Although corona ry artery disease is common in patients with the insulin resistance sy ndrome, the effects of troglitazone on smooth muscle cells (SMC) have not been fully elucidated. We therefore examined the effects of trogli tazone on cell growth and glucose uptake in human aortic SMC. Mitogen- activated protein (MAP) kinase activity and glucose transporter (Glut) 1 mRNA levels were also studied. In the absence of troglitazone, insu lin (10(-7) M) caused a 2-fold increase of DNA synthesis in SMC and tr oglitazone suppressed the increase of DNA synthesis in a dose-dependen t manner. This growth suppression was accompanied by inhibition of MAP kinase activity. On the other hand, troglitazone significantly increa sed Glut 1 mRNA and enhanced glucose uptake in SMC. These results sugg est that troglitazone affects the insulin signaling pathways in SMC an d suppresses growth while promoting glucose uptake. Our findings suppo rt the application of troglitazone as an inhibitor of SMC proliferatio n in patients with insulin resistance. (C) 1998 Elsevier Science Irela nd Ltd.