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

Nobukata, Hidefumi; Ishikawa, Tsutomu; Obata, Masaomi; Shibutani, Yasunori

doi:10.1053/meta.2000.6739

Cited by 36 publications

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“…These results indicate that EPA-E inhibits ADP-or collageninduced platelet aggregation by causing an increase in platelet membrane fluidity. The above-mentioned results coincided with our previous data obtained in WBN/Kob rats treated with EPA-E [10]. In contrast, it became evident that lard, increasing the insulin resistance in OLETF rats, did not increase or decrease the above-mentioned parameters in this study.…”

Section: Discussionsupporting

confidence: 93%

“…Recently, we demonstrated that the long-term administration of EPA-E improves hyperglycemia, insulin resistance, and blood coagulation abnormalities in WBN/Kob rats, a model of spontaneous diabetes mellitus [10]. In the present study, we investigated whether the longterm treatment of EPA-E would ameliorate blood coagulation abnormalities and dysfunction of vascular endothelial and cells in OLETF rats, a model of spontaneous non-insulin-dependent diabetes mellitus with obesity.…”

Section: Discussionmentioning

confidence: 89%

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Long-Term Administration of Highly Purified Eicosapentaenoic Acid Ethyl Ester Improves Blood Coagulation Abnormalities and Dysfunction of Vascular Endothelial Cells in Otsuka Long-Evans Tokushima Fatty Rats

et al. 2003

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Abstract. We investigated the effect of highly purified eicosapentaenoic acid ethyl ester (EPA-E) on blood coagulation abnormalities and dysfunction of vascular endothelial cells in spontaneously diabetic Otsuka Long-Evans Tokushima Fatty rats. The animals were treated with either EPA-E or lard at a daily dose of 0.3 g/kg/day for 52 weeks by gavage, and their coagulation/fibrinolytic parameters, platelet aggregation, and functions of the vascular endothelial cells were examined. EPA-E significantly improved coagulation-related parameters including prothrombin time, activated partial thromboplastin time, fibrinogen level, and activities of factor II, V, VII, VIII, IX, X, XI, and XII, and antithrombin III, and fibrinolysis-related parameters including plasminogen, tissue-type plasminogen activator, a 2 -plasmin inhibitor, and plasminogen activator inhibitor. It also suppressed ADP-or collagen-induced platelet aggregation and the cholesterol/ phospholipid molar ratio in platelet membranes at a dose of 0.3 g/kg. In addition, it significantly increased the migration activity of vascular endothelial cells, and decreased the binding of vascular endothelial cells to vascular endothelial growth factor. In contrast, lard had no effect on hypercoagulation, hypofibrinolysis, and platelet hyperaggregation but significantly aggravated the dysfunction of vascular endothelial cells. These data demonstrate that EPA-E beneficially altered certain factors known to promote thrombosis and atherosclerosis in this animal model. WE reported previously that the long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid, which has an inhibitory effect on platelet aggregation and lipid-lowering effect, causes an improvement of insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of spontaneous noninsulin-dependent diabetes mellitus with obesity [1] and that of high sucrose-induced insulin resistance in Dahl salt-sensitive (Dahl-S) rats [2]. It is well recognized that hyperglycemia enhances many risk factors for arteriosclerosis and works as a thrombus-forming factor via causing blood coagulation abnormalities and dysfunction of vascular endothelial cells and thrombocytes [3,4]. Thus, in the present study, we investigated the effect of EPA-E on blood coagulation abnormalities and

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 89%

Long-Term Administration of Highly Purified Eicosapentaenoic Acid Ethyl Ester Improves Blood Coagulation Abnormalities and Dysfunction of Vascular Endothelial Cells in Otsuka Long-Evans Tokushima Fatty Rats

et al. 2003

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“…Metformin, a biguanide, is known to improve insulin resistance in the clinical setting (11), and inhibition of fatty liver is believed to play a role in this (28,29). Polyunsaturated fatty acids have been reported to prevent fatty liver and to improve insulin resistance (30,31) via several mechanisms, including inhibition of the expression of lipogenic enzymes (32) by hindering binding of LXR to LXRE (33) to inhibit transcription of SREBP-1, and decrease in the content of triglycerides in the liver by enhancement of beta-oxidation of fatty acids through activation of PPARα (34). The suppression of expression of SREBP-1 by atorvastatin observed in this study suggests the possibility that atorvastatin decreases fat synthesis by decreasing the activity of lipogenic enzymes including FAS.…”

Section: Discussionmentioning

confidence: 99%

Effects of Atorvastatin on Glucose Metabolism and Insulin Resistance in KK/Ay Mice

Suzuki

Kakuta²,

Takahashi

et al. 2005

JAT

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“…This difference between the two diets might have been due to the higher presence in HFD2 of precursors for ω3 polyunsaturated fatty acid (i.e. α-linolenic acid), which are known to protect from insulin resistance (Nobukata et al, 2000;Carpentier et al, 2006). At any rate, the different time-course of hyperglycemia with HFD1 and HFD2 allowed us to correlate some of the effects observed with the two diets on EC levels to the development of hyperglycemia or obesity.…”

Section: Composition Of the Hfdsmentioning

confidence: 99%

Dysregulation of peripheral endocannabinoid levels in hyperglycemia and obesity: Effect of high fat diets

Matias

Petrosino

Racioppi

et al. 2008

Molecular and Cellular Endocrinology

148

125

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Please cite this article as: Matias, I., Petrosino, S., Racioppi, A., Capasso, R., Izzo, A.A., Di Marzo, V., Dysregulation of peripheral endocannabinoid levels in hyperglycemia and obesity: effect of high fat diets, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. elevations (in the skeletal muscle, heart and kidney) or reductions (in the thyroid) of the levels of either AEA or 2-AG, or both, were found. Depending on the diet, these changes preceded or accompanied the development of overt obesity and/or hyperglycemia. In the adrenal gland, first a reduction and then an elevation of EC levels were observed. In the brown fat, a very early elevation of both AEA and 2-AG normalized levels was observed with one of the diets, whereas delayed decreases appeared to be caused by an increase of the amount of fat tissue weight induced by the HFDs. The potential implications of these and previous findings in the general framework of the proposed roles of the EC system in the control of metabolic, endocrine and cardiovascular and renal functions are discussed.

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

Cited by 36 publications

References 0 publications

Long-Term Administration of Highly Purified Eicosapentaenoic Acid Ethyl Ester Improves Blood Coagulation Abnormalities and Dysfunction of Vascular Endothelial Cells in Otsuka Long-Evans Tokushima Fatty Rats

Long-Term Administration of Highly Purified Eicosapentaenoic Acid Ethyl Ester Improves Blood Coagulation Abnormalities and Dysfunction of Vascular Endothelial Cells in Otsuka Long-Evans Tokushima Fatty Rats

Effects of Atorvastatin on Glucose Metabolism and Insulin Resistance in KK/Ay Mice

Dysregulation of peripheral endocannabinoid levels in hyperglycemia and obesity: Effect of high fat diets

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