Influence of highly purified eicosapentaenoic acid ethyl ester on insulin resistance in the Otsuka Long-Evans Tokushima Fatty Rat, a model of spontaneous non-insulin-dependent diabetes mellitus

Mori, Yutaka; Murakawa, Yûichi; Katoh, Shūichi; Hata, Shoichi; Yokoyama, Jun′ichi; Tajima, Naoko; Ikeda, Yoshio; Nobukata, Hidefumi; Ishikawa, Tsutomu; Shibutani, Yasunori

doi:10.1016/s0026-0495(97)90148-7

Cited by 82 publications

(57 citation statements)

References 15 publications

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“…Furthermore, it is of great interest that tyrosine phosphorylation of IRS-1 is specific for EPA, since other fatty acids cannot induce tyrosine phosphorylation of IRS-1. These findings are consistent with recent reports that EPA improves insulin sensitivity (1)(2)(3)(4). Moreover, it is our surprise that EPA inhibited MAPK activity as well as proliferation of HepG2 cells.…”

Section: Resultssupporting

confidence: 93%

Dual Action of Eicosapentaenoic Acid in Hepatoma Cells

Morimoto¹,

Kaji²,

Iida³

et al. 2001

Journal of Biological Chemistry

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Exogenous administration of eicosapentaenoic acid (EPA) improves insulin sensitivity, but its precise mechanism remains unknown. Here we show that EPA stimulates the intracellular insulin signaling pathway in hepatoma cells. Exposure of these cells to EPA caused up-regulation of several insulin-induced activities including tyrosine phosphorylation of insulin receptor substrate-1, insulin receptor substrate-1-associated phosphatidylinositol 3-kinase, and its downstream target Akt kinase activity as well as down-regulation of gluconeogenesis. In contrast, EPA decreased mitogenactivated protein kinase activity and inhibited cell proliferation. These findings raise the possibility that EPA up-regulates metabolic action of insulin and inhibits cell growth in humans.

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Section: Resultssupporting

confidence: 93%

Dual Action of Eicosapentaenoic Acid in Hepatoma Cells

Morimoto¹,

Kaji²,

Iida³

et al. 2001

Journal of Biological Chemistry

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“…The mechanisms through which long-chain nÀ3 fatty acids may affect glucose metabolism include their incorporation into the phospholipids of plasma membranes, which increases the fluidity of the membranes and modulates the properties of membrane proteins mediating insulin action (Borkman et al, 1993;Liu et al, 1994;Mori et al, 1997). In the present study, we observed higher plasma EPA in female Ala-allele carriers than in Pro/Pro females.…”

Section: Discussionsupporting

confidence: 56%

The Pro12Ala polymorphism of the PPAR-γ2 gene affects associations of fish intake and marine n−3 fatty acids with glucose metabolism

Ylonen

Salminen

Lyssenko³

et al. 2007

Eur J Clin Nutr

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Background/Objectives: Data on associations between marine nÀ3 fatty acids and glucose metabolism are inconsistent. Therefore, we explored effects of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor (PPAR)-g2 gene on associations of fish intake and dietary and plasma eicosapentaenoic and docosahexaenoic acid with glucose metabolism. The design comprises of the cross-sectional analysis. Subjects/Methods: The Pro12Ala variant in the PPAR-g2 (PPARG) gene was genotyped in 571 non-diabetic relatives of subjects with type II diabetes. The dietary intake was measured by a 3-day food record, and the plasma cholesterol ester fatty acid composition was analysed with gas chromatography. Associations of dietary and plasma variables with insulin resistance and fasting and 2-h glucose and free fatty acid concentrations were analysed with multiple linear regression analysis. Results: In men, there was a significant interaction between PPARG polymorphism and plasma docosahexaenoic acid on fasting free fatty acid concentration (P ¼ 0.036), and genotype-stratified models showed an inverse association in Pro homozygotes only (P ¼ 0.028). In women, the proportion of plasma eicosapentaenoic acid was higher in Ala-allele carriers compared to Pro homozygotes (1.67 vs 1.44% respectively, P ¼ 0.006). A significant interaction between PPARG polymorphism and fish intake on 2-h glucose was found in women (P ¼ 0.021), and genotype-stratified models suggested an inverse association in Ala-allele carriers only (P ¼ 0.039). Conclusions: The findings suggest that PPARG polymorphism might affect the plasma proportion of eicosapentaenoic acid and modulate the associations of fish intake and marine nÀ3 fatty acids with glucose metabolism and fasting free fatty acids.

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“…EPA and DHA rich oil prevented insulin resistance and hypertension in a fructosefed rat model (Huang et al, 1997). Purified EPA ethyl ester reduced insulin resistance and decreased the incidence of type 2 DM in OLETF and WBN=Kob rats respectively (models of spontaneous type 2 DM) by modifying the phospholipid fatty acid composition of the skeletal membrane (Mori et al, 1997;Nobukata et al, 2000). The observation that (a) there is a significant correlation between insulin secretion and action and AA (Pelikanova et al, 1989), (b) an inverse relationship exists between fasting plasma insulin and the percentage of AA in erythrocyte fatty acids (Clifton & Nestel, 1998), and (c) decreased insulin sensitivity is associated with decreased concentrations of PUFAs in skeletal muscle phospholipids in normal men (Borkman et al, 1993) suggests that PUFAs can modulate insulin sensitivity and insulin resistance.…”

Section: Lcpufas and Type 2 Diabetes Mellitusmentioning

confidence: 99%

Can perinatal supplementation of long-chain polyunsaturated fatty acids prevent diabetes mellitus?

Das¹

2003

Eur J Clin Nutr

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It is suggested that the negative correlation between breast-feeding and insulin resistance and diabetes mellitus can be related to the presence of significant amounts of long-chain polyunsaturated fatty acids in the human breast milk. Based on this, it is proposed that provision of adequate amounts of long chain polyunsaturated fatty acids during the critical periods of brain growth and development can prevent or postpone the development diabetes mellitus.

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Influence of highly purified eicosapentaenoic acid ethyl ester on insulin resistance in the Otsuka Long-Evans Tokushima Fatty Rat, a model of spontaneous non-insulin-dependent diabetes mellitus

Cited by 82 publications

References 15 publications

Dual Action of Eicosapentaenoic Acid in Hepatoma Cells

Dual Action of Eicosapentaenoic Acid in Hepatoma Cells

The Pro12Ala polymorphism of the PPAR-γ2 gene affects associations of fish intake and marine n−3 fatty acids with glucose metabolism

Can perinatal supplementation of long-chain polyunsaturated fatty acids prevent diabetes mellitus?

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