ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways
Journal article
Lee, Hye Jeong, Moon, Jiyoung, Chung, InHyeok, Chung, Ji Hyung, Park, Chan, Lee, Jung Ok, Han, Jeong Ah, Kang, Min Ju, Yoo, Eun Hye, Kwak, So-Young, Jo, Garam, Park, Wonil, Park, Jonghoon, Kim, Kyoung Min, Lim, Soo, Ngoei, Kevin R. W., Ling, Naomi X. Y., Oakhill, Jonathan S., Galic, Sandra, ... Kim, Hyeon Soo. (2019). ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways. The FASEB Journal. 33(12), pp. 14825 - 14840. https://doi.org/10.1096/fj.201901440RR
Authors | Lee, Hye Jeong, Moon, Jiyoung, Chung, InHyeok, Chung, Ji Hyung, Park, Chan, Lee, Jung Ok, Han, Jeong Ah, Kang, Min Ju, Yoo, Eun Hye, Kwak, So-Young, Jo, Garam, Park, Wonil, Park, Jonghoon, Kim, Kyoung Min, Lim, Soo, Ngoei, Kevin R. W., Ling, Naomi X. Y., Oakhill, Jonathan S., Galic, Sandra, Murray-Segal, Lisa, Kemp, Bruce E., Mantzoros, Christos S., Krauss, Ronald M., Shin, Min-Jeong and Kim, Hyeon Soo |
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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 skeletalmuscle cells and in exercized mice and healthy men. IF1 stimulates glucose uptake viaAMPKin skeletalmuscle cells and primary culturedmyoblasts.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 inhibitsATPhydrolysis byb-F1-ATPase inplasmamembrane, 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 amechanismby 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. |
Keywords | diabetes; glucose uptake |
Year | 2019 |
Journal | The FASEB Journal |
Journal citation | 33 (12), pp. 14825 - 14840 |
Publisher | Federation of American Societies for Experimental Biology |
ISSN | 1530-6860 |
Digital Object Identifier (DOI) | https://doi.org/10.1096/fj.201901440RR |
Scopus EID | 2-s2.0-85076066452 |
Page range | 14825 - 14840 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | File Access Level Controlled |
Place of publication | United States of America |
https://acuresearchbank.acu.edu.au/item/8q66q/atp-synthase-inhibitory-factor-1-if1-a-novel-myokine-regulates-glucose-metabolism-by-ampk-and-akt-dual-pathways
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