title: Importance of cyclooxygenase 2-mediated low-grade inflammation in the development of fructose-induced insulin resistance in rats.
abstract: This study was designed to examine the role of cyclooxygenase (COX) 2-mediated low-grade inflammation in the development of fructose-induced whole body and muscular insulin resistance in rats. The rats were on regular or fructose-enriched diets for 8 weeks. Fructose-fed rats were further divided into 3 groups (n = 8 per group). There were fructose-fed rats, fructose-fed rats with nimesulide (a selective COX2 inhibitor, 30 mg/kg/day, gavage) and fructose-fed rats with celecoxib (a selective COX2 inhibitor, 30 mg/kg/day, gavage). The present result showed that fructose-induced time-dependent increases in systolic blood pressure and fasting plasma insulin and triglyceride levels were significantly suppressed in rats treated with nimesulide or cerecoxib. The ratio of area under glucose curve divided by area under insulin curve obtained during the oral glucose tolerance test was significantly decreased in fructose-fed rats, which were markedly reversed in those co-treated with nimesulide or celecoxib. Accordingly, fructose-induced decrease in insulin-stimulated glucose uptake in soleus muscle was significantly reversed in those combined with nimesulide or celecoxib. Fructose-induced time-dependent increases in plasma 8-isoprostane and PGE metabolites were concomitantly suppressed by nimesulide or celecoxib co-treatment. The present study demonstrates that the COX2-mediated low-grade inflammation, especially mediated by increase in oxidative stress was important in the development of insulin resistance in fructose-fed rats.
authors.affiliation: Department of Family and Community, Hualien Army Force Hospital, Hualien, Taiwan, Republic of China.
authors.forename: Tse-Tsung
authors.initials: TT
authors.lastname: Liu
authors.forename: Kuang-Chung
authors.initials: KC
authors.lastname: Shih
authors.forename: Chung-Cheng
authors.initials: CC
authors.lastname: Kao
authors.forename: Wei-Tung
authors.initials: WT
authors.lastname: Cheng
authors.forename: Po-Shiuan
authors.initials: PS
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000276:immunology* / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D005632:Fructose / Q000633:toxicity; D005947:Glucose / Q000493:pharmacokinetics; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000276:immunology*; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D018482:Muscle, Skeletal / Q000378:metabolism; D011458:Prostaglandins E / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013549:Sweetening Agents / Q000633:toxicity
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D011458:Prostaglandins E; D013549:Sweetening Agents; C075750:8-epi-prostaglandin F2alpha; D005632:Fructose; D015237:Dinoprost; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D005947:Glucose