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 (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.

Effect of downhill walking on next-day muscle damage and glucose metabolism in healthy young subjects.

This study aimed to investigate the effect of downhill walking on muscle damage and glucose metabolism in healthy subjects. All ten healthy young men and women (age, 24.0 ± 1.4 years) performed rest, uphill walking, and downhill walking trials. In the exercise trials, uphill (+ 5%) or downhill (- 5%) treadmill walking was performed at 6 km/h for 30 min. On the next day, muscle soreness was significantly higher in the downhill trial than in the uphill trial (P < 0.01). Respiratory metabolic performance did not differ between trials. However, carbohydrate oxidation was negatively correlated with plasma creatine kinase (r = - 0.41) and muscle soreness (r = - 0.47). Fasting blood glucose was significantly lower in the uphill trial than in the rest trial (P < 0.01) but not in the downhill trial. These observations suggest that downhill but not uphill walking causes mild delayed-onset muscle damage, which did not cause marked impairment in glucose metabolism. However, higher muscle damage responders might exhibit lower glucose metabolism.