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Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP-activated protein kinase activation.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2019 Sep; Vol. 33 (9), pp. 10551-10562. Date of Electronic Publication: 2019 Jun 21. - Publication Year :
- 2019
-
Abstract
- During exercise, skeletal muscles release cytokines, peptides, and metabolites that exert autocrine, paracrine, or endocrine effects on glucose homeostasis. In this study, we investigated the effects of secreted protein acidic and rich in cysteine (SPARC), an exercise-responsive myokine, on glucose metabolism in human and mouse skeletal muscle. SPARC-knockout mice showed impaired systemic metabolism and reduced phosphorylation of AMPK and protein kinase B in skeletal muscle. Treatment of SPARC-knockout mice with recombinant SPARC improved glucose tolerance and concomitantly activated AMPK in skeletal muscle. These effects were dependent on AMPK-γ3 because SPARC treatment enhanced skeletal muscle glucose uptake in wild-type mice but not in AMPK-γ3-knockout mice. SPARC strongly interacted with the voltage-dependent calcium channel, and inhibition of calcium-dependent signaling prevented SPARC-induced AMPK phosphorylation in human and mouse myotubes. Finally, chronic SPARC treatment improved systemic glucose tolerance and AMPK signaling in skeletal muscle of high-fat diet-induced obese mice, highlighting the efficacy of SPARC treatment in the management of metabolic diseases. Thus, our findings suggest that SPARC treatment mimics the effects of exercise on glucose tolerance by enhancing AMPK-dependent glucose uptake in skeletal muscle.-Aoi, W., Hirano, N., Lassiter, D. G., Björnholm, M., Chibalin, A. V., Sakuma, K., Tanimura, Y., Mizushima, K., Takagi, T., Naito, Y., Zierath, J. R., Krook, A. Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP-activated protein kinase activation.
- Subjects :
- AMP-Activated Protein Kinases genetics
Animals
Diet, High-Fat adverse effects
Female
Glucose Intolerance metabolism
Glucose Intolerance pathology
Homeostasis
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle, Skeletal metabolism
Obesity etiology
Obesity metabolism
Phosphorylation
Signal Transduction
AMP-Activated Protein Kinases metabolism
Glucose metabolism
Glucose Intolerance prevention & control
Muscle, Skeletal pathology
Obesity prevention & control
Osteonectin physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 33
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 31225998
- Full Text :
- https://doi.org/10.1096/fj.201900453R