Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP-activated protein kinase activation
Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP-activated protein kinase activation
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DOI：
10.1096/fj.201900453r
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发表时间：
2019-09-01
期刊：
影响因子：
4.8
通讯作者：
Krook, Anna
中科院分区：
文献类型：
--
作者：
Aoi, Wataru;Hirano, Nariyuki;Krook, Anna
在运动中，骨骼肌释放细胞因子、多肽和代谢物，对葡萄糖稳态产生自分泌、旁分泌或内分泌作用。在这项研究中，我们研究了富含半胱氨酸的酸性分泌蛋白(SPARC)对人和小鼠骨骼肌糖代谢的影响。SPARC基因敲除的小鼠表现出全身代谢受损，骨骼肌中AMPK和蛋白激酶B的磷酸化水平降低。用重组SPARC治疗SPARC基因敲除小鼠可改善糖耐量并同时激活骨骼肌中的AMPK。这些效应依赖于AMPK-Gamma 3，因为SPARC治疗增加了野生型小鼠的骨骼肌葡萄糖摄取，而不是AMPK-Gamma 3基因敲除小鼠。SPARC与电压依赖性钙通道有很强的相互作用，抑制钙依赖性信号可阻止SPARC诱导的人和小鼠肌管AMPK的磷酸化。最后，慢性SPARC治疗改善了高脂饮食诱导的肥胖小鼠全身糖耐量和骨骼肌AMPK信号，突显了SPARC治疗在管理代谢性疾病方面的有效性。因此，我们的研究结果表明，SPARC治疗通过提高骨骼肌对AMPK依赖的葡萄糖摄取来模拟运动对葡萄糖耐量的影响。-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.分泌型酸性和富含半胱氨酸的蛋白(SPARC)通过AMP激活的蛋白激酶激活改善葡萄糖耐量。
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-gamma 3 because SPARC treatment enhanced skeletal muscle glucose uptake in wild-type mice but not in AMPK-gamma 3-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.