Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP-activated protein kinase activation.

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 an exercise-responsive myokine, on glucose metabolism in human and mouse skeletal muscle. mice showed impaired systemic metabolism and reduced phosphorylation of AMPK and protein kinase B in skeletal muscle. Treatment of duanyu1842RC-knockout mice with recombinant improved glucose tolerance and concomitantly activated AMPK in skeletal muscle. These effects were dependent on AMPK-γ3 because duanyu1842RC treatment enhanced skeletal muscle glucose uptake in wild-type mice but not in AMPK-γ3-knockout mice. duanyu1842RC strongly interacted with the voltage-dependent calcium channel, and inhibition of calcium-dependent signaling prevented AMPK phosphorylation in human and mouse myotubes. Finally, chronic duanyu1842RC treatment improved systemic glucose tolerance and AMPK signaling in skeletal muscle of high-fat diet-induced obese mice, highlighting the efficacy of duanyu1842RC treatment in the management of metabolic diseases. Thus, our findings suggest that duanyu1842RC 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 improves glucose tolerance via AMP-activated protein kinase activation.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}