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ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways
- Source :
- The FASEB Journal. 33:14825-14840
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
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.
- Subjects :
- Adult
Male
0301 basic medicine
Glucose uptake
Carbohydrate metabolism
Biochemistry
Cell Line
Myoblasts
Mice
03 medical and health sciences
chemistry.chemical_compound
Adenosine Triphosphate
0302 clinical medicine
AMP-Activated Protein Kinase Kinases
Myokine
Genetics
Animals
Humans
Hypoglycemic Agents
Interleukin 6
Molecular Biology
Protein kinase B
Cells, Cultured
diabetes
ATP synthase
biology
Proteins
AMPK
Recombinant Proteins
glucose uptake
Cell biology
Mice, Inbred C57BL
Glucose
030104 developmental biology
Diabetes Mellitus, Type 2
chemistry
biology.protein
Protein Kinases
Proto-Oncogene Proteins c-akt
Adenosine triphosphate
030217 neurology & neurosurgery
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....655061dcd4be4daf675d76cc26fa325d