Importance of Cyclooxygenase 2-Mediated Low-Grade Inflammation in Development of Fructose-Induced Insulin Resistance in Rats

10.4077/CJP.2009.AMH034

Tse-Tsung Liu；Kuang-Chung Shih；Chung-Cheng Kao；Wei-Tung Cheng；Po-Shiuan Hsieh

cyclooxygenase 2-mediated inflammation ； oxidative stress ； fructose ； skeletal muscle ； insulin resistance ； rats

The Chinese Journal of Physiology

52卷2期（2009 / 04 / 01）

7 - 13

英文

This study was designed to examine the role of COX2-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.

1. Hsieh, P.S.,Cheng, W.T.,Liu, T.T.,Loh, C.H.,Chang, B.C.,Hsieh, P.-S.,Cheng, W.-T.,Liu, T.-T.,Loh, C.-H.,Chang, B.-C.(2007).Diminution of hypertriglyceridemia-induced pressor effect under hyperinsulinemic condition in normal and fructose-induced insulin resistant rats.Chinese. J. Physiol.,50,99-104.
   連結：
2. Alpert, E.,Gruzman, A.,Tennenbaum, T.,Sasson, S.(2007).Selective cyclooxygenase-2 inhibitors stimulate glucose transport in L6 myotubes in a protein kinase C [delta]-dependent manner.Biochem. Pharmacol.,73,368-377.
3. Ariano, M.A.,Armstrong, R.B.,Edgerton, V.R.(1973).Hindlimb muscle fiber populations of five mammals.J. Histochem. Cytochem.,21,51-55.
4. Camps, M.,Castello, A.,Munoz, P.,Monfar, M.,Testar, X.,Palacin, M,Zorzano, A.(1992).Effect of diabetes and fasting on GLUT-4 (muscle/fat) glucose-transporter expression in insulinsensitive tissues. Heterogeneous response in heart, red and white muscle.Biochem. J.,282,765-772.
5. Davi, G.,Catalano, I.,Averna, M.,Notarbartolo, A.,Strano, A.,Ciabattoni, G.,Patrono, C.(1990).Thromboxane biosynthesis and platelet function in type II diabetes mellitus.N. Engl. J. Med.,322,1769-1774.
6. Davi, G.,Ciabattoni, G.,Consoli, A.,Mezzetti, A.,Falco, A.,Santarone, S.,Pennese, E.,Vitacolonna, E.,Bucciarelli, T.,Costantini, F.,Capani, F.,Patrono, C.(1999).In Vivo Formation of 8-iso-prostaglandin F2{alpha} and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation.Circulation,99,224-229.
7. Duncan, B.B.,Schmidt, M.I.,Pankow, J.S.,Ballantyne, C.M.,Couper, D.,Vigo, A.,Hoogeveen, R.,Folsom, AR.,Heiss, G.(2003).Low-grade systemic inflammation and the development of type 2 Diabetes: the Atherosclerosis Risk in Communities study.Diabetes,52,1799-1805.
8. El Midaoui, A.,Wu, R. and de,Champlain, J.(2002).Prevention of hypertension, hyperglycemia and vascular oxidative stress by aspirin treatment in chronically glucose-fed rats.J. Hypertens.,20,1407-1412.
9. Eriksson, J.W.(2007).Metabolic stress in insulin's target cells leads to ROS accumulation-a hypothetical common pathway causing insulin resistance.FEBS Lett.,581,3734-3742.
10. FitzGerald, G.A.,Patrono, C.(2001).The coxibs, selective inhibitors of cyclooxygenase-2.New England Journal of Medicine,345,433-442.
11. Galipeau, D.,Arikawa, E.,Sekirov, I.,McNeill, J.H.(2001).Chronic thromboxane synthase inhibition prevents fructose-induced hypertension.Hypertension,38,872-876.
12. Gonzalez-Ortiz, M.,Martinez-Abundis, E.,Balcazar-Munoz, B.R.,Robles-Cervantes, J.A.(2001).Inhibition of cyclooxygenase-1 or -2 on insulin sensitivity in healthy subjects.Horm. Metab. Res.,33,250-253.
13. Hansen, P.A.,Gulve, E.A.,Holloszy, J.O.(1994).Suitability of 2-deoxyglucose for in vitro measurement of glucose transport activity in skeletal muscle.J Appl. Physiol.,76,979-985.
14. Helmersson, J.,Vessby, B.,Larsson, A.,Basu, S.(2004).Association of Type 2 Diabetes With Cyclooxygenase-Mediated Inflammation and Oxidative Stress in an Elderly Population.Circulation,109,1729-1734.
15. Henriksen, E.J.,Bourey, R.E.,Rodnick, K.J.,Koranyi, L.,Permutt, M.A.,Holloszy, J.O.(1990).Glucose transporter protein content and glucose transport capacity in rat skeletal muscles.Am. J. Physiol.,259,593-598.
16. Hermann, M.,Camici, G.,Fratton, A.,Hurlimann, D.,Tanner, F.C.,Hellermann, J.P.,Fiedler, M.,Thiery, J.,Neidhart, M.,Gay, R.E.,Gay, S.,Luscher, T.F.,Ruschitzka, F.(2003).Differential efects of selective cyclooxygenase-2 inhibitors on endothelial function in salt-induced hypertension.Circulation,108,2308-2311.
17. Hsieh, P.S.(2004).Attenuation of insulin-mediated pressor effect and nitric oxide release in rats with fructose-induced insulin resistance.Am. J. Hypertens.,17,707-711.
18. Hsieh, P.S.(2005).Reversal of fructose-induced hypertension and insulin resistance by chronic losartan treatment is independent of AT2 receptor activation in rats.J. Hypertens.,23,2209-2217.
19. Huang, Y.,Liu, J.,Wang, L-z.,Zhang, W.-y.,Zhu, X.-z.(2005).Neuroprotective effects of cyclooxygenase-2 inhibitor celecoxib against toxicity of LPS-stimulated macrophages toward motor neurons.Acta Pharmacol. Sin.,26,952-958.
20. Hundal, R.S.,Petersen, K.F.,Mayerson, A.B.,Randhawa, P.S.,Inzucchi, S.,Shoelson, S.E.,Shulman, G.I.(2002).Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes.J Clin. Invest.,109,1321-1326.
21. Kern, M.,Wells, J.A,Stephens, J.M.,Elton, C.W.,Friedman, J.E.,Tapscott, E.B.,Pekala, P.H.,Dohm, G.L.(1990).Insulin responsiveness in skeletal muscle is determined by glucose transporter (Glut4) protein level.Biochem. J.,270,397-400.
22. Konheim, Y.L.,Wolford, J.K.(2003).Association of a promoter variant in the inducible cyclooxygenase-2 gene (PTGS2) with type 2 diabetes mellitus in Pima Indians.Hum. Genet.,113,377-381.
23. McAdam, B.F.,Catella-Lawson, F.,Mardini, I.A.,Kapoor, S.,Lawson, J.A.,FitzGerald, GA.(1999).Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: The human pharmacology of a selective inhibitor of COX-2.Proc. Natl. Acad. Sci. U.S. A.,96,272-277.
24. Meszaros, K.,Lang, C.H.,Bagby, G.J.,Spitzer, J.J.(1987).Contribution of different organs to increased glucose consumption after endotoxin administration.J. Biol. Chem.,262,10965-10970.
25. Miller, A.,Adeli, K.,Miller, A.,Adeli, K.(2008).Dietary fructose and the metabolic syndrome.Curr. Opin. Gastroenterol.,24,204-209.
26. Perucca, E.(1993).Drug interactions with nimesulide.Drugs,46(1),79-82.
27. Pitt, B.,Pepine, C.,Willerson, J.T.(2002).Cyclooxygenase-2 inhibition and cardiovascular events.Circulation,106,167-169.
28. Pradhan, A.D.,Manson, J.E.,Rifai, N.,Buring, J.E.,Ridker, P.M.(2001).C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus.J. Am. Med. Assoc.,286,327-334.
29. Rutledge, A.C.,Adeli, K.,Rutledge, A.C.,Adeli, K.(2007).Fructose and the metabolic syndrome: pathophysiology and molecular mechanisms.Nutr. Rev.,65,13-23.
30. Schmidt, M.I.,Duncan, B.B.(2003).Diabesity: an inflammatory metabolic condition.Clin. Chem. Lab. Med.,41,1120-1130.
31. Smith, C.J.,Zhang, Y.,Koboldt, C.M.,Muhammad, J.,Zweifel, B.S.,Shaffer, A.,Talley, J.J.,Masferrer, J.L.,Seibert, K.,Isakson, P.C.(1998).Pharmacological analysis of cyclooxygenase-1 in inflammation.Proc. Natl. Acad. Sci. U.S.A.,95,13313-13318.
32. Sone, H.,Takahashi, A.,Yamada, N.(2001).Ibuprofen-related hypoglycemia in a patient receiving sulfonylurea.Ann. Intern. Med.,134,344.
33. Taddei, S.,Virdis, A.,Ghiadoni, L.,Magagna, A.,Salvetti, A.(1998).Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension.Circulation,97,2222-2229.
34. Whelton, A.,Schulman, G.,Wallemark, C.,Drower, E.J.,Isakson, P. C.,Verburg, K.M.,Geis, G.S.(2000).Effects of celecoxib and naproxen on renal function in the elderly.Arch. Intern. Med.,160,1465-1470.
35. Whittington, K.B.,Solomon, S.S.,Lu, Z.N.,Selawry, H.P.(1991).Islet allografts in the cryptorchid testes of spontaneously diabetic BB/Wor dp rats: response to glucose, glipizide, and arginine.Endocrinology,128,2671-2677.
36. Young, D.A.,Uhl, J.J.,Cartee, G.D.,Holloszy, J.O.(1986).Activation of glucose transport in muscle by prolonged exposure to insulin. Effects of glucose and insulin concentrations.J. Biol. Chem.,261,16049-16053.