Troglitazone enhances glycolysis and improves intracellular glucose metabolism in rat mesangial cells.
To clarify the action of the new antidiabetic agent, troglitazone, on rat mesangial cells, we assessed its effect on the uptake and intracellular metabolism of glucose. Troglitazone increased the uptake of 2-deoxyglucose (2DOG) in a dose-dependent manner with an upregulation of glucose transporter 1 (GLUT1) mRNA, whereas it had no effect on the uptake of alpha-methyl glucoside (AMG). This troglitazone-induced glucose uptake was not suppressed by phlorizin. In 5 mmol/L glucose, 2 microg/mL (4.5 micromol/L) troglitazone increased glucose consumption 2.9-fold, similar to that in 20 mmol/L glucose. Troglitazone increased the production of pyruvate and lactate as a consequence of the increase in glycolysis, but did not increase the cellular ATP content. Troglitazone improved the high-glucose-induced accumulation of intracellular sorbitol and fructose and elevation of the cellular redox potential. These data suggest that troglitazone enhances glucose uptake through GLUT1 with an acceleration of glycolysis, and improves the abnormal intracellular glucose metabolism under high-glucose conditions in rat mesangial cells.
Asano
T
T
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Wakisaka
M
M
Yoshinari
M
M
Nakamura
S
S
Doi
Y
Y
Fujishima
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D006019:Glycolysis / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008757:Methylglucosides / Q000493:pharmacokinetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D010695:Phlorhizin / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013012:Sorbitol / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014158:Transcription, Genetic / Q000187:drug effects; D000077288:Troglitazone
D002839:Chromans; D051272:Glucose Transporter Type 1; D007004:Hypoglycemic Agents; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D013844:Thiazoles; D045162:Thiazolidinediones; D013012:Sorbitol; C027020:methylglucoside; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D010695:Phlorhizin; D000077288:Troglitazone; D005947:Glucose