Long-term administration of highly purified eicosapentaenoic acid ethyl ester prevents diabetes and abnormalities of blood coagulation in male WBN/Kob rats

We investigated the effect of long-term administration of highly purified e icosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid , on the development of diabetes, insulin resistance, and abnormalities of blood coagulation in male WBN/Kob rats, a model of spontaneous diabetes mel litus. After 8-month oral EPA-E treatment, the incidence of diabetes at a d ose of 0.1, 0.3, and 1.0 g/kg was 92%, 50%, and 17%, respectively. Its inci dence was suppressed significantly and dose-dependently at a dose of 0.3 g/ kg or higher compared with the rate (100%) for the vehicle control. Additio nally, EPA-E significantly and dose-dependently decreased the elevation of plasma glucose after an oral glucose load and increased the glucose infusio n rate (GIR) during the euglycemic insulin-glucose clamp test at a dose of 0.1 g/kg or higher compared with the vehicle control. Furthermore, EPA-E si gnificantly and dose-dependently ameliorated coagulation related parameters , including the prothrombin time (PT), activated partial thromboplastin tim e (APTT), fibrinogen level, and factor II, V,VII, VIII, IX, X, XI, and XII and antithrombin III (AT III) activities, and fibrinolysis-related paramete rs, including plasminogen, tissue-type plasminogen activator (t-PA), alpha( 2)-plasmin inhibitor (alpha(2)-PI), and plasminogen activator inhibitor (PA I), and also suppressed ADP- or collagen-induced platelet aggregation and t he cholesterol to phospholipid (C/P) molar ratio in platelet membranes at a dose of 0.1 g/kg or higher. These data demonstrate multiple actions of the product in these laboratory animals. These include changes in platelet fun ction, coagulation/fibrinolysis factors, plasma immunoreactive insulin secr etion, and plasma glucose/insulin resistance. Copyright (C) 2000 by W.B. Sa unders Company.