Roles of Interleukin 17 in Angiotensin II Type 1 Receptor-Mediated Insulin Resistance

被引：49
作者：
Ohshima, Kousei [1 ,2 ]
Mogi, Masaki [1 ]
Jing, Fei [1 ]
Iwanami, Jun [1 ]
Tsukuda, Kana [1 ]
Min, Li-Juan [1 ]
Higaki, Jitsuo [2 ]
Horiuchi, Masatsugu [1 ]
机构：
[1] Ehime Univ, Grad Sch Med, Dept Mol Cardiovasc Biol & Pharmacol, Tohon, Ehime 7910295, Japan
[2] Ehime Univ, Grad Sch Med, Dept Integrated Med & Informat, Tohon, Ehime 7910295, Japan
来源：
HYPERTENSION | 2012年 / 59卷 / 02期
关键词：
low-grade inflammation; interleukin; 17; insulin resistance; angiotensin II type 1 receptor blocker; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE-CELLS; ALDOSTERONE SYSTEM; GENE-EXPRESSION; GLUCOSE-UPTAKE; HUMAN OBESITY; T-CELLS; MICE; INFLAMMATION; ADIPOGENESIS;
D O I：
10.1161/HYPERTENSIONAHA.111.183178
中图分类号：
R6 [外科学];
学科分类号：
1002 ; 100210 ;
摘要：
Interleukin 17 (IL-17) is known to contribute to the pathogenesis of hypertension, atherosclerosis, and adipocyte differentiation; however, the roles of IL-17 in glucose metabolism remain to be elucidated. Angiotensin II type 1 receptor blockers improve insulin resistance at least in part because of the amelioration of inflammation. Therefore, we examined the possible roles of IL-17 in the pathogenesis of insulin resistance in type 2 diabetes mellitus using a mouse model, KK-Ay, and angiotensin II type 1 receptor-mediated insulin resistance. KK-Ay mice were administered control-IgG(2A) or anti-IL-17 antibody 5 times at a dose of 100 mu g every second day by IP injection. KK-Ay mice were administered telmisartan for 2 weeks. C57BL/6J mice treated with angiotensin II infusion for 2 weeks were administered telmisartan or hydralazine. Insulin resistance was evaluated by oral glucose tolerance test, insulin tolerance test, and uptake of 2-[H-3]deoxy-D-glucose in peripheral tissues. Serum IL-17 concentration in KK-Ay mice was significantly higher than that in C57BL/6J mice. Treatment of KK-Ay mice with anti-IL-17 antibody significantly increased 2-[H-3]deoxy-D-glucose uptake in skeletal muscle but not in white adipose tissue and attenuated the increase in blood glucose level after a glucose load. Blockade of IL-17 enhanced the expression of adipocyte differentiation markers and adiponectin. Treatment with telmisartan decreased serum IL-17 concentration in KK-Ay and ameliorated angiotensin II-induced insulin resistance with a decrease in serum IL-17 level in C57BL/6J. In conclusion, IL-17 could play an important role in the pathogenesis of angiotensin II type 1 receptor-induced insulin resistance. (Hypertension. 2012;59[part 2]:493-499.). Online Data Supplement
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页码：493 / +
页数：10
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