Differential effect of the antidiabetic thiazolidinediones troglitazone and pioglitazone on human platelet aggregation mechanism.

• T Ishizuka

  Third Department of Internal Medicine, Gifu University School of Medicine, Japan. [e-mail]

• S Itaya

  Third Department of Internal Medicine, Gifu University School of Medicine, Japan. [e-mail]

• H Wada

  Third Department of Internal Medicine, Gifu University School of Medicine, Japan. [e-mail]

• M Ishizawa

  Third Department of Internal Medicine, Gifu University School of Medicine, Japan. [e-mail]

• M Kimura

  Third Department of Internal Medicine, Gifu University School of Medicine, Japan. [e-mail]

• K Kajita

  Third Department of Internal Medicine, Gifu University School of Medicine, Japan. [e-mail]

• Y Kanoh

  Third Department of Internal Medicine, Gifu University School of Medicine, Japan. [e-mail]

• A Miura

  Third Department of Internal Medicine, Gifu University School of Medicine, Japan. [e-mail]

• N Muto

  Third Department of Internal Medicine, Gifu University School of Medicine, Japan. [e-mail]

• K Yasuda

  Third Department of Internal Medicine, Gifu University School of Medicine, Japan. [e-mail]

抄録

Troglitazone and pioglitazone, antidiabetic thiazolidinediones, are known to improve insulin resistance. However, the effect of these drugs on platelet aggregation remains unclear. The chemical structure of troglitazone contains vitamin E. Accordingly, we studied the effect of troglitazone, pioglitazone, and vitamin E on thrombin-induced platelet aggregation, metabolism of phosphoinositide, protein phosphorylation, protein kinase C (PKC)-alpha and -beta, and phosphatidylinositol (PI) 3-kinase activation in vitro in human platelets. Maximum platelet aggregation by ADP, collagen, and thrombin decreased in the presence of 0.1-1 micromol/l troglitazone and 500 nmol/l vitamin E for 60 min compared with controls. However, pioglitazone did not inhibit ADP-, collagen-, or thrombin-induced platelet aggregation. Pretreatment with troglitazone and vitamin E, but not with pioglitazone, resulted in decreases in thrombin-induced phosphatidic acid production, hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C, and 47-kDa protein phosphorylation. Thrombin-induced PKC-alpha and -beta activation in membrane fraction was suppressed by pretreatment with troglitazone and vitamin E, but not with pioglitazone. Separately, troglitazone and pioglitazone stimulated PI 3-kinase activity, but thrombin-induced PI 3-kinase activation was suppressed by pretreatment with troglitazone and pioglitazone for 60 min. These results suggest that troglitazone and vitamin E, but not pioglitazone, have a potent inhibitory effect on platelet aggregation via suppression of the thrombin-induced activation of phosphoinositide signaling in human platelets. Finally, the chemical structure of vitamin E may contribute to the inhibitory effect of troglitazone on platelet aggregation in human platelets.

収録刊行物

• Diabetes

  Diabetes 47 (9), 1494-1500, 1998-09-01

  American Diabetes Association

キーワード

• Endocrinology, Diabetes and Metabolism
• Internal Medicine

詳細情報

• CRID: 1360855570878708992
• NII論文ID: 30026271308
• NII書誌ID: AA00628057
• DOI: 10.2337/diabetes.47.9.1494
• ISSN: 1939327X
• ISSN: 00121797
• ISSN: http://id.crossref.org/issn/00121797
• Web Site: https://journals.org/diabetes/diabetes/article-pdf/47/9/1494/363714/9726240.pdf
• Web Site: https://diabetesjournals.org/diabetes/article-pdf/47/9/1494/363714/9726240.pdf
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