Ethyl icosapentate (omega-3 fatty acid) causes accumulation of lipids in skeletal muscle but suppresses insulin resistance in OLETF rats. Otsuka Long-Evans Tokushima Fatty.

摘要

Ethyl icosapentate (EPA) is known to improve insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM); however, its mechanism is unclear. In this study, we attempted to determine the mechanism of EPA's effects on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Administration of EPA caused a reduction in plasma cholesterol and triglycerides, but increased cholesterol and triglyceride contents in skeletal muscle. EPA did not have an effect on glucose or insulin levels. EPA accelerated the glucose infusion rate (GIR) and improved the endothelium-dependent relaxation of OLETF rat the thoracic aorta caused by addition of acetylcholine. However, the improvement observed in endothelium-dependent relaxation disappeared after addition of N(w)-nitro-L-arginine (L-NA). Furthermore, when L-NA and indomethacine were added to the medium, relaxation of the aorta in EPA-treated rats was weaker than that in control rats. These actions may cause NO induction in the endothelium and an increase in prostaglandin I(2) (PGI(2)) and prostaglandin I(3) (PGI(3)) action, which in turn may result in improvement of insulin resistance.