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We observed that the hyperinsulinemic-euglycemic clamp test, in vivo glucose uptake by PET and the hepatic [corrected] Akt signaling. Immunofluorescence was performed to examine the distribution and localization of ER stress molecules and insulin signaling molecules. Expression of phospho-Akt, phospho-IRS1, and phospho-p70S6K was significantly decreased in the livers of high-fat diet-fed mice compared with those fed with a standard diet. Immunofluorescence staining revealed that glucose transporter 2 (Glut2) and phosphorylated insulin receptor substrate 1 (pIRS1) in liver endothelial cells (LECs) were colocalized with Vimentin, as confirmed by co-localization. Analysis of the activation of the ER stress signaling molecule phosphorylated eukaryotic initiation factor 2 α (p-eIF2α) showed a significant increase in the number of LECs with a positive staining for p-eIF2α. Next, we examined the effects of inhibiting the ER stress signaling pathway on the insulin resistance induced by high-fat diet. Treatment of LECs with 4-phenylbutyrate, an ER stress inhibitor, significantly improved the insulin resistance induced by a high-fat diet in vitro. The results of this study suggest that ER stress molecules are involved in high-fat diet-induced endothelial insulin resistance in the liver through their localization to LECs. Furthermore, we propose that liver endothelial ER stress is an important therapeutic target for the treatment of hepatic insulin resistance induced by a high-fat diet.Acute myeloid leukaemia (AML) is a blood cancer that affects the cells of the bone marrow, and is often fatal. It usually occurs in older people, who are more likely System Requirements: This mod does not have any special requirements for your Operating System but they are recommended to run the mod. You might have to install the Filesystem Mod in order to load the addon. 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