title: Inhibitory effect of glyburide on thrombin-induced platelet aggregation and phosphoinositide metabolism in normal human platelets.
abstract: We previously reported the effects of diet, sulphonylureas or insulin on thrombin-induced platelet aggregation, phosphoinositide metabolism and protein phosphorylation in non-insulin-dependent diabetes mellitus (NIDDM) patients. To clarify the mechanism of glyburide and insulin on platelet function, here we studied the in vitro effects of glyburide and insulin on thrombin-induced metabolic changes using normal human platelets. Platelet aggregation stimulated with <0.5 U/ml thrombin, 0.75-3 microM adenosine diphosphate (ADP) or 1 microg/ml collagen was significantly lower in glyburide-treated platelets, but not in insulin-treated platelets, than in untreated ones (control). Thrombin-induced incorporation of 32P radioactivity into phosphatidic acid (PA) in glyburide-treated platelets was lower than that in control but not in insulin-treated platelets. Phosphorylated proteins of platelets induced by thrombin and 12- O -tetradecanoylphorbol 13-acetate (TPA) in glyburide-treated platelets were suppressed, but not in insulin-treated platelets, compared with control. These results suggest that glyburide induces suppression of thrombin-induced activation of phospholipase C, which mediates hydrolysis of PIP and PIP(2) and production of PA, and subsequently inhibits platelet aggregation.
authors.affiliation: The Third Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: T
authors.initials: T
authors.lastname: Ishizuka
authors.forename: S
authors.initials: S
authors.lastname: Itaya
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Kajita
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: A
authors.initials: A
authors.lastname: Miura
authors.forename: T
authors.initials: T
authors.lastname: Shibata
authors.forename: Y
authors.initials: Y
authors.lastname: Kanoh
authors.forename: M
authors.initials: M
authors.lastname: Ishizawa
authors.forename: K
authors.initials: K
authors.lastname: Yasuda