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

Takada, Shingo; Hirabayashi, Kagami; Kinugawa, Shintaro; Yokota, Takashi; Matsushima, Shouji; Suga, Tadashi; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Mizushima, Wataru; Masaki, Yoshihiro; Furihata, Takaaki; Katsuyama, Ryoichi; Okita, Koichi; Tsutsui, Hiroyuki

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

Takada, Shingo; Hirabayashi, Kagami; Kinugawa, Shintaro et al.

European Journal of Pharmacology, 2014, 740, 690-696

Permalink : https://hdl.handle.net/2115/57270

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アクセス権	open access
URI	https://hdl.handle.net/2115/57270
タイトル	Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice
著者	Takada, Shingo ; Hirabayashi, Kagami ; Kinugawa, Shintaro ; Yokota, Takashi ; Matsushima, Shouji ; Suga, Tadashi ; Kadoguchi, Tomoyasu ; Fukushima, Arata ; Homma, Tsuneaki ; Mizushima, Wataru ; Masaki, Yoshihiro ; Furihata, Takaaki ; Katsuyama, Ryoichi ; Okita, Koichi ; Tsutsui, Hiroyuki
e-Rad_Researcher 60722329 著者名 Takada, Shingo
著者名 Hirabayashi, Kagami
e-Rad_Researcher 60399871 著者名 Kinugawa, Shintaro
e-Rad_Researcher 90374321 著者名 Yokota, Takashi
著者名 Matsushima, Shouji
e-Rad_Researcher 30708673 著者名 Suga, Tadashi
著者名 Kadoguchi, Tomoyasu
e-Rad_Researcher 40706553 著者名 Fukushima, Arata
著者名 Homma, Tsuneaki
著者名 Mizushima, Wataru
著者名 Masaki, Yoshihiro
e-Rad_Researcher 60782505 著者名 Furihata, Takaaki
著者名 Katsuyama, Ryoichi
e-Rad_Researcher 80382539 著者名 Okita, Koichi
e-Rad_Researcher 70264017 著者名 Tsutsui, Hiroyuki
言語	英語
キーワード	Insulin resistance
	Diabetes
	Mitochondria
	Muscle
	Oxidative stress
発行日	2014-10-05
出版者	Elsevier
収録物名	European Journal of Pharmacology
巻(号)	740
ページ	690-696
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0014-2999
関連情報	PMID 24964389
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.ejphar.2014.06.008