title: (Pro)renin receptor in skeletal muscle is involved in the development of insulin resistance associated with postinfarct heart failure in mice.
abstract: We previously reported that insulin resistance was induced by the impairment of insulin signaling in the skeletal muscle from heart failure (HF) via NAD(P)H oxidase-dependent oxidative stress. (Pro)renin receptor [(P)RR] is involved in the activation of local renin-angiotensin system and subsequent oxidative stress. We thus examined whether (P)RR inhibitor, handle region peptide (HRP), could ameliorate insulin resistance in HF after myocardial infarction (MI) by improving oxidative stress and insulin signaling in the skeletal muscle. C57BL6J mice were divided into four groups: sham operated (Sham, n = 10), Sham treated with HRP (Sham+HRP, 0.1 mg·kg(-1)·day(-1), n = 10), MI operated (MI, n = 10), and MI treated with HRP (MI+HRP, 0.1 mg/kg/day, n = 10). After 4 wk, MI mice showed left ventricular dysfunction, which was not affected by HRP. (P)RR was upregulated in the skeletal muscle after MI (149% of sham, P < 0.05). The decrease in plasma glucose after insulin load was smaller in MI than in Sham (21 ± 2 vs. 44 ± 3%, P < 0.05), and was greater in MI+HRP (38 ± 2%, P < 0.05) than in MI. Insulin-stimulated serine phosphorylation of Akt and glucose transporter 4 translocation were decreased in the skeletal muscle from MI by 48 and 49% of Sham, both of which were ameliorated in MI+HRP. Superoxide production and NAD(P)H oxidase activities were increased in MI, which was inhibited in MI+HRP. HRP ameliorated insulin resistance associated with HF by improving insulin signaling via the inhibition of NAD(P)H oxidase-induced superoxide production in the skeletal muscle. The (P)RR pathway is involved in the development of insulin resistance, at least in part, via the impairment of insulin signaling in the skeletal muscle from HF.
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors: Arata
authors: A
authors: Fukushima
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan; tuckahoe@med.hokudai.ac.jp.
authors: Shintaro
authors: S
authors: Kinugawa
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan; Research Fellow of the Japan Society for the Promotion of Science, Tokyo, Japan; and.
authors: Shingo
authors: S
authors: Takada
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors: Shouji
authors: S
authors: Matsushima
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan; Diponegoro University, Semarang, Indonesia;
authors: Mochamad Ali
authors: MA
authors: Sobirin
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors: Taisuke
authors: T
authors: Ono
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors: Masashige
authors: M
authors: Takahashi
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan; Research Fellow of the Japan Society for the Promotion of Science, Tokyo, Japan; and.
authors: Tadashi
authors: T
authors: Suga
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors: Tsuneaki
authors: T
authors: Homma
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors: Yoshihiro
authors: Y
authors: Masaki
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors: Takaaki
authors: T
authors: Furihata
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors: Tomoyasu
authors: T
authors: Kadoguchi
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors: Takashi
authors: T
authors: Yokota
authors: Graduate School of Program in Lifelong Learning Studies, Hokusho University, Ebetsu, Japan.
authors: Koichi
authors: K
authors: Okita
authors: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
authors: Hiroyuki
authors: H
authors: Tsutsui
mesh_terms: D000808:Angiotensinogen / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002460:Cell Line; D004562:Electrocardiography; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D007150:Immunohistochemistry; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology*; D019255:NADPH Oxidases / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction; D000093342:Prorenin Receptor
chemical_list: D007328:Insulin; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D000808:Angiotensinogen; D019255:NADPH Oxidases; D051058:Oncogene Protein v-akt; D000093342:Prorenin Receptor
keywords: (pro)renin receptor; heart failure; insulin resistance; oxidative stress; renin-angiotensin system