Indomethacin Activates Peroxisome Proliferator-activated Receptor γ to Improve Insulin Resistance in Cotton Pellet Granuloma Model

被引：6

作者：

Wu, H-T ^{[3
]}

Chen, W. ^{[4
,5
]}

Cheng, K-C ^{[6
]}

Yeh, C-H ^{[7
]}

Shen, K-H ^{[1
,2
]}

Cheng, J-T ^{[1
,2
,3
,7
]}

机构：

[1] Chi Mei Med Ctr, Dept Med Res, Yong Kang City 73101, Tainan County, Taiwan

[2] Chi Mei Med Ctr, Dept Urol, Yong Kang City 73101, Tainan County, Taiwan

[3] Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 70101, Taiwan

[4] E Da Hosp, Dept Internal Med, Kaohsiung Cty, Taiwan

[5] I Shou Univ, Kaohsiung Cty, Taiwan

[6] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Psychosomatr Internal Med, Kagoshima 890, Japan

[7] Chang Jung Christian Univ, Coll Hlth Sci, Inst Med Sci, Guei Ren, Tainan County, Taiwan

来源：

HORMONE AND METABOLIC RESEARCH | 2010年 / 42卷 / 11期

关键词：

cotton pellet granuloma; diabetes; indomethacin; insulin resistance; nitric oxide; peroxisome proliferator-activated receptor gamma; prostaglandin E2; ADIPOSE-TISSUE; OXIDATIVE STRESS; TNF-ALPHA; OBESITY; INFLAMMATION; EXPRESSION; ASSOCIATION; MECHANISMS; MICE;

D O I：

10.1055/s-0030-1261952

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Inflammation is involved in the development of insulin resistance and diabetes. However, the effectiveness of anti-inflammatory drugs in diabetic therapy remains obscure. In the present study, the possible mechanisms of indomethacin, one of the nonsteroidal anti-inflammatory drugs, in the improvement of insulin resistance were investigated. Indomethacin treatment significantly decreased cotton pellet implantation induced white blood cell count elevation and immune cells infiltration in epididymal white adipose tissue. Also, cotton pellet implantation induced impaired glucose utilization and insulin resistance were improved by indomethacin. The decrement in phosphoinsulin receptor and phospho-Akt levels induced by cotton pellet implantation was improved by indomethacin as well. Moreover, indomethacin decreased cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in epididymal white adipose tissue with a marked reduction of prostaglandin 2 (PGE2) and nitrite/nitrate (NOx) levels in cotton pellet-implanted mice. Furthermore, pretreatment of peroxisome proliferator-activated receptor gamma (PPAR gamma) antagonist, GW9662 not only reversed indomethacin-modified COX-2 and iNOS levels but also reversed indomethacin-improved insulin sensitivity determined by homeostasis model assessment-insulin resistance (HOMA-IR). Taken together, indomethacin might elevate the expression of PPAR gamma to decrease serum NOx and PGE2 to result in the improvement of insulin resistance.

引用

页码：775 / 780

页数：6

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