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ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways

Authors
Lee, Hye JeongMoon, JiyoungChung, InHyeokChung, Ji HyungPark, ChanLee, Jung OkHan, Jeong AhKang, Min JuYoo, Eun HyeKwak, So-YoungJo, GaramPark, WonilPark, JonghoonKim, Kyoung MinLim, SooNgoei, Kevin R. W.Ling, Naomi X. Y.Oakhill, Jonathan S.Galic, SandraMurray-Segal, LisaKemp, Bruce E.Mantzoros, Christos S.Krauss, Ronald M.Shin, Min-JeongKim, Hyeon Soo
Issue Date
12월-2019
Publisher
WILEY
Keywords
diabetes; glucose uptake
Citation
FASEB JOURNAL, v.33, no.12, pp.14825 - 14840
Indexed
SCIE
SCOPUS
Journal Title
FASEB JOURNAL
Volume
33
Number
12
Start Page
14825
End Page
14840
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/61457
DOI
10.1096/fj.201901440RR
ISSN
0892-6638
Abstract
ATPase inhibitory factor 1 (IF1) is an ATP synthase interacting protein that suppresses the hydrolysis activity of ATP synthase. In this study, we observed that the expression of IF1 was up-regulated in response to electrical pulse stimulation of skeletal muscle cells and in exercized mice and healthy men. IF1 stimulates glucose uptake via AMPK in skeletal muscle cells and primary cultured myoblasts. Reactive oxygen species and Rac family small GTPase 1 (Rac1) function in the upstream and downstream of AMPK, respectively, in IF1-mediated glucose uptake. In diabetic animal models, the administration of recombinant IF1 improved glucose tolerance and down-regulated blood glucose level. In addition, IF1 inhibits ATP hydrolysis by beta-F1-ATPase in plasma membrane, thereby increasing extracellular ATP and activating the protein kinase B (Akt) pathway, ultimately leading to glucose uptake. Thus, we suggest that IF1 is a novel myokine and propose a mechanism by which AMPK and Akt contribute independently to IF1-mediated improvement of glucose tolerance impairment. These results demonstrate the importance of IF1 as a potential antidiabetic agent.
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College of Education > Department of Physical Education > 1. Journal Articles
College of Health Sciences > School of Biosystems and Biomedical Sciences > 1. Journal Articles
Graduate School > Department of Biomedical Sciences > 1. Journal Articles

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