| 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 |
| Diabetes |
| Mitochondria |
| Muscle |
| 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) |
| URI: | http://hdl.handle.net/2115/57270 |
| 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)
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