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Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP‐activated protein kinase activation
Author(s) -
Aoi Wataru,
Hirano Nariyuki,
Lassiter David G.,
Björnholm Marie,
Chibalin Alexander V.,
Sakuma Kunihiro,
Tanimura Yuko,
Mizushima Katsura,
Takagi Tomohisa,
Naito Yuji,
Zierath Juleen R.,
Krook Anna
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900453r
Subject(s) - cysteine , protein kinase a , chemistry , amp activated protein kinase , biochemistry , microbiology and biotechnology , cgmp dependent protein kinase , kinase , mitogen activated protein kinase kinase , biology , ampk , enzyme
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. FASEB J. 33, 10551–10562 (2019). www.fasebj.org