Carboxylated and uncarboxylated forms of osteocalcin directly modulate the glucose transport system and inflammation in adipocytes.
Carboxylated and uncarboxylated forms of osteocalcin directly modulate the glucose transport system and inflammation in adipocytes.
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DOI：
10.1055/s-0034-1368709
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Garvey WT
中科院分区：
文献类型：
--
作者：
Hill HS;Grams J;Walton RG;Liu J;Moellering DR;Garvey WT
骨钙素由成骨细胞分泌，可改善体内胰岛素敏感性，但机制尚不清楚。我们测试了骨钙素直接调节胰岛素靶向外周组织中的细胞生物学的假设。在 L-6 肌细胞中，无论在胰岛素不存在（基础）还是存在的情况下，骨钙素都会刺激葡萄糖转运。同样，在原代培养的脂肪细胞中，羧化和非羧化骨钙素均增加基础和胰岛素刺激的葡萄糖转运以及胰岛素敏感性。骨钙素还增加基础和胰岛素刺激的葡萄糖氧化，但对脂肪酸合成或脂肪分解没有影响。在原代培养的脂肪细胞中，两种形式的骨钙素均抑制肿瘤坏死因子α向培养基中的分泌。然而，只有羧化骨钙素抑制白细胞介素6的释放，并且两种形式的骨钙素都不能调节单核细胞趋化蛋白1的分泌。羧化和非羧化骨钙素均增加脂联素和抗炎细胞因子白介素 10 的分泌。总之，羧化和非羧化骨钙素均直接增加脂肪细胞和肌肉细胞中的葡萄糖转运，同时抑制促炎细胞因子分泌并刺激白细胞介素 10 和脂联素释放。因此，这些结果提供了骨钙素的胰岛素增敏作用的机制，并有助于阐明骨在调节全身代谢中的作用。
Osteocalcin is secreted by osteoblasts and improves insulin sensitivity in vivo, although mechanisms remain unclear. We tested the hypothesis that osteocalcin directly modulates cell biology in insulin-targeted peripheral tissues. In L-6 myocytes, osteocalcin stimulated glucose transport both in the absence (basal) and presence of insulin. Similarly, in primary cultured adipocytes, both carboxylated and uncarboxylated osteocalcin increased basal and insulin-stimulated glucose transport as well as insulin sensitivity. Osteocalcin also increased basal and insulin-stimulated glucose oxidation, though there was no effect on fatty acid synthesis or lipolysis. In primary-cultured adipocytes, both forms of osteocalcin suppressed secretion of tumor necrosis factor alpha into the media; however, only carboxylated osteocalcin suppressed interleukin 6 release, and neither form of osteocalcin modulated monocyte chemoattractant protein-1 secretion. Both carboxylated and uncarboxylated osteocalcin increased secretion of adiponectin and the anti-inflammatory cytokine interleukin 10. In conclusion, both carboxylated and uncarboxylated osteocalcin directly increase glucose transport in adipocytes and muscle cells, while suppressing proinflammatory cytokine secretion and stimulating interleukin 10 and adiponectin release. Thus, these results provide a mechanism for the insulin-sensitizing effects of osteocalcin and help elucidate the role that bone plays in regulating systemic metabolism.