Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP-activated protein kinase activation
| Autor: | Juleen R. Zierath, Katsura Mizushima, Wataru Aoi, Alexander V. Chibalin, David G. Lassiter, Yuko Tanimura, Anna Krook, Tomohisa Takagi, Kunihiro Sakuma, Marie Björnholm, Yuji Naito, Nariyuki Hirano |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
biology Chemistry Glucose uptake AMPK Skeletal muscle Biochemistry Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure AMP-activated protein kinase Myokine Genetics biology.protein medicine Glucose homeostasis Phosphorylation Molecular Biology Protein kinase B 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | The FASEB Journal. 33(No. 9):10551-10562 |
| Popis: | 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., Bjornholm, 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. |
| Databáze: | OpenAIRE |
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