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.
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.
Kusunoki
Masataka
M
First Department of Internal Medicine, Aichi Medical University, Aichi, Japan.
Tsutsumi
Kazuhiko
K
Hara
Tsutomu
T
Ogawa
Hitoshi
H
Nakamura
Takao
T
Miyata
Tetsuo
T
Sakakibara
Fumihiko
F
Fukuzawa
Yoshitaka
Y
Suga
Takashi
T
Kato
Koichi
K
Hirooka
Yoshitumi
Y
Nakaya
Yutaka
Y
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D020334:Rats, Inbred OLETF; D014664:Vasodilation / Q000187:drug effects
D001786:Blood Glucose; D015525:Fatty Acids, Omega-3; D007328:Insulin; D008055:Lipids