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Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice

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Title: Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice
Authors: Takada, Shingo Browse this author →KAKEN DB
Hirabayashi, Kagami Browse this author
Kinugawa, Shintaro Browse this author →KAKEN DB
Yokota, Takashi Browse this author →KAKEN DB
Matsushima, Shouji Browse this author
Suga, Tadashi Browse this author →KAKEN DB
Kadoguchi, Tomoyasu Browse this author
Fukushima, Arata Browse this author →KAKEN DB
Homma, Tsuneaki Browse this author
Mizushima, Wataru Browse this author
Masaki, Yoshihiro Browse this author
Furihata, Takaaki Browse this author →KAKEN DB
Katsuyama, Ryoichi Browse this author
Okita, Koichi Browse this author →KAKEN DB
Tsutsui, Hiroyuki Browse this author →KAKEN DB
Keywords: Insulin resistance
Oxidative stress
Issue Date: 5-Oct-2014
Publisher: Elsevier
Journal Title: European Journal of Pharmacology
Volume: 740
Start Page: 690
End Page: 696
Publisher DOI: 10.1016/j.ejphar.2014.06.008
PMID: 24964389
Abstract: We have reported that exercise capacity is reduced in high fat diet (HFD)-induced diabetic mice, and that this reduction is associated with impaired mitochondrial function in skeletal muscle (SKM). However, it remains to be clarified whether the treatment of diabetes ameliorates the reduced exercise capacity. Therefore, we examined whether an insulin sensitizing drug, pioglitazone, could improve exercise capacity in HFD mice. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated with or without pioglitazone (3 mg/kg/day) to yield the following 4 groups: ND+vehicle, ND+pioglitazone, FLED I vehicle, and HFD+pioglitazone (n=10 each). After 8 weeks, body weight, plasma glucose, and insulin in the HFD+vehicle were significantly increased compared to the ND I vehicle group. Pioglitazone normalized the insulin levels in RED fed mice, but did not affect the body weight or plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in the HFD+vehicle, and this reduction was almost completely ameliorated in HFD+pioglitazone mice. ADP dependent mitochondrial respiration, complex l and Ill activities, and citrate synthase activity were significantly decreased in the SKM of the HFD+vehicle animals, and these decreases were also attenuated by pioglitazone. NAD(P)H oxidase activity was significantly increased in the HFD+vehicle compared with the ND+vehicle, and this increase was ameliorated in HFD+pioglitazone mice. Pioglitazone improved the exercise capacity in diabetic mice, which was due to the improvement in mitochondria! function and attenuation of oxidative stress in the SKM. Our data suggest that pioglitazone may be useful as an agent for the treatment of diabetes mellitus. (C) 2014 Elsevier B.V. All rights reserved.
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 高田 真吾

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