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

Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, Japan.
Hypertension (Impact Factor: 6.48). 12/2011; 59(2):493-9. DOI: 10.1161/HYPERTENSIONAHA.111.183178
Source: PubMed


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 μg 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-[(3)H]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-[(3)H]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.

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    • "The levels of circulating cytokines produced during chronic low-grade inflammation might be sufficient to contribute to pancreatic beta-cell failure in early T2D (Dula et al. 2010), and IL-17 was shown to promote production of proinflammatory cytokines and directly cause betacell dysfunction in vitro (Arif et al. 2011; Miljkovic and Trajkovic 2004; Miljkovic et al. 2005; Onishi and Gaffen 2010). The prodiabetogenic potential of IL-17 is further suggested by its role in the pathogenesis of angiotensin II type 1 receptor-induced insulin resistance in a mouse model of T2D (Ohshima et al. 2012). Also, IL-17 was implicated in T2D-associated local inflammatory reactions , such as chronic periodontitis (Santos et al. 2010), as well as in development of functional and phenotypic alterations in blood vessels contributing to development of hypertension, atherosclerosis and ischemic coronary disease (Cheng et al. 2008; Hashmi and Zeng 2006; Madhur et al. 2010). "
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