HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Hokkaido University Hospital >
Peer-reviewed Journal Articles, etc >

Direct renin inhibitor ameliorates insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice

Creative Commons License

Files in This Item:
EurJPharmacol779_147.pdf656.94 kBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/65354

Title: Direct renin inhibitor ameliorates insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice
Authors: Fukushima, Arata Browse this author →KAKEN DB
Kinugawa, Shintaro Browse this author →KAKEN DB
Takada, Shingo Browse this author →KAKEN DB
Matsumoto, Junichi Browse this author
Furihata, Takaaki Browse this author →KAKEN DB
Mizushima, Wataru Browse this author
Tsuda, Masaya Browse this author
Yokota, Takashi Browse this author →KAKEN DB
Matsushima, Shouji Browse this author
Okita, Koichi Browse this author →KAKEN DB
Tsutsui, Hiroyuki Browse this author →KAKEN DB
Keywords: Direct renin inhibitor
Insulin resistance
Heart failure
Skeletal muscle
Oxidative stress
(Pro)renin receptor
Issue Date: 15-May-2016
Publisher: Elsevier
Journal Title: European journal of pharmacology
Volume: 779
Start Page: 147
End Page: 156
Publisher DOI: 10.1016/j.ejphar.2016.03.022
PMID: 26988296
Abstract: Insulin resistance can occur as a consequence of heart failure (HF). Activation of the renin-angiotensin system (RAS) may play a crucial role in this phenomenon. We thus investigated the effect of a direct renin inhibitor, aliskiren, on insulin resistance in HF after myocardial infarction (MI). MI and sham operation were performed in male C57BL/6 J mice. The mice were divided into 4 groups and treated with sham-operation (Sham, n=10), sham-operation and aliskiren (Sham+Aliskiren; 10 mg/kg/day, n=10), MI (n=11), or MI and aliskiren (MI+Aliskiren, n=11). After 4 weeks, MI mice showed left ventricular dilation and dysfunction, which were not affected by aliskiren. The percent decrease of blood glucose after insulin load was significantly smaller in MI than in Sham (14±5% vs. 36±2%), and was ameliorated in MI+Aliskiren (34±5%) mice. Insulin-stimulated serine-phosphorylation of Akt and glucose transporter 4 translocation were decreased in the skeletal muscle of MI compared to Sham by 57% and 69%, and both changes were ameliorated in the MI+Aliskiren group (91% and 94%). Aliskiren administration in MI mice significantly inhibited plasma renin activity and angiotensin II (Ang II) levels. Moreover, (pro)renin receptor expression and local Ang II production were upregulated in skeletal muscle from MI and were attenuated in MI+Aliskiren mice, in tandem with a decrease in superoxide production and NAD(P)H oxidase activities. In conclusion, aliskiren ameliorated insulin resistance in HF by improving insulin signaling in the skeletal muscle, at least partly by inhibiting systemic and (pro)renin receptor-mediated local RAS activation, and subsequent NAD(P)H oxidase-induced oxidative stress.
Rights: © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/65354
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 福島 新

Export metadata:

OAI-PMH ( junii2 , jpcoar )


 

Feedback - Hokkaido University