title: Roles of interleukin 17 in angiotensin II type 1 receptor-mediated insulin resistance.
abstract: 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.
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, Japan.
authors.forename: Kousei
authors.initials: K
authors.lastname: Ohshima
authors.forename: Masaki
authors.initials: M
authors.lastname: Mogi
authors.forename: Fei
authors.initials: F
authors.lastname: Jing
authors.forename: Jun
authors.initials: J
authors.lastname: Iwanami
authors.forename: Kana
authors.initials: K
authors.lastname: Tsukuda
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Min
authors.forename: Jitsuo
authors.initials: J
authors.lastname: Higaki
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D020381:Interleukin-17 / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology*; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000888:Antibodies, Anti-Idiotypic; D001562:Benzimidazoles; D001565:Benzoates; D020381:Interleukin-17; D044140:Receptor, Angiotensin, Type 1; D005947:Glucose; D000077333:Telmisartan