Troglitazone enhances glucose uptake and inhibits mitogen-activated protein kinase in human aortic smooth muscle cells.
The thiazolidinedione analogue troglitazone is an antidiabetic agent that improves insulin resistance in rodents and humans. Although coronary artery disease is common in patients with the insulin resistance syndrome, the effects of troglitazone on smooth muscle cells (SMC) have not been fully elucidated. We therefore examined the effects of troglitazone 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, insulin (10(-7) M) caused a 2-fold increase of DNA synthesis in SMC and troglitazone suppressed the increase of DNA synthesis in a dose-dependent manner. This growth suppression was accompanied by inhibition of MAP kinase activity. On the other hand, troglitazone significantly increased Glut 1 mRNA and enhanced glucose uptake in SMC. These results suggest that troglitazone affects the insulin signaling pathways in SMC and suppresses growth while promoting glucose uptake. Our findings support the application of troglitazone as an inhibitor of SMC proliferation in patients with insulin resistance.
Kihara
S
S
Second Department of Internal Medicine, Osaka University Medical School, Suita, Japan.
Ouchi
N
N
Funahashi
T
T
Shinohara
E
E
Tamura
R
R
Yamashita
S
S
Matsuzawa
Y
Y
D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D001161:Arteriosclerosis / Q000201:enzymology / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D005947:Glucose / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000077288:Troglitazone; D005947:Glucose