Effect of Pioglitazone on Insulin Receptors from Skeletal Muscle of High Fat-Fed Rats.
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A new oral agent, 5-[4-[2 (5-ethyl 12-pyridyl) ethoxy]-benzoyl]-2, 4-thiazo lidinedione pioglitazone, has been developed for treatment of NIDDM. We examined its offectiveness in high fat-fed rats with insulin resistance. Administration of the agent (10mg/day/kg) for two weeks decreased hyperlipidemia and hyperinsulinemia, indicating that the agent increases insulin sensitivity in vivo in high fat-fed rast. To clarify the mechanism by which the drug increases insulin sensitivity, we examined the insulin binding and kinase activity of insulin receptors form muscles of rats fed with either a high fat or non-high fat diet. Pioglitazone treatment did not change insulin binding in the high fat-fed rats, but it increased insulin-stimulated autophosphorylation of insulin receptors to the level of the control group. Although kinase activity toward an exogenous substrate, poly Glu<SUP>4</SUP>Tyr<SUP>1</SUP>, tended to increase to the level of the control animals, The difference was not significant. These results suggest that pioglitazone increases insulin sensitivity in part by activating autophosphorylation of the receptors and that the drug appears to be a useful one, with a new mode of action for treating the insulin resistance in NIDDM.
- 一般社団法人 日本糖尿病学会の論文
一般社団法人 日本糖尿病学会 | 論文
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