Pioglitazone ameliorates high glucose induced desensitization of insulin receptor kinase in Rat 1 fibroblasts in culture.
A new oral agent, pioglitazone, increases insulin sensitivity by activating receptor kinase in insulin-resistant rats. To clarify the mechanism, we studied in vitro effects of glucose and pioglitazone on the insulin receptor function using Rat 1 fibroblasts which expressed human insulin receptors. Insulin receptor kinase activity was impaired by incubating cells for 4 days in the presence of 27mM D-glucose. The glucose effect was time- and dose-dependent and also specific for D-glucose, since D-raffinose incubation had no effect. Pioglitazone treatment did not have any effect on intact receptor kinase. However, exposure of both 27mM D-glucose and 0.1 microM pioglitazone to the cells completely prevented the glucose-induced impairment of insulin receptor kinase activity, suggesting that pioglitazone might reverse the processes which are critical for the glucose-induced desensitization of insulin receptor kinase.
Maegawa
H
H
Third Department of Medicine, Shiga University of Medical Science, Japan.
Tachikawa-Ide
R
R
Ugi
S
S
Iwanishi
M
M
Egawa
K
K
Kikkawa
R
R
Shigeta
Y
Y
Kashiwagi
A
A
D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005947:Glucose / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007700:Kinetics; D010766:Phosphorylation; D000077205:Pioglitazone; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000302:isolation & purification / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones
D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D005947:Glucose; D000077205:Pioglitazone