FoxO1 expression in osteoblasts regulates glucose homeostasis through regulation of osteocalcin in mice
FoxO1 expression in osteoblasts regulates glucose homeostasis through regulation of osteocalcin in mice
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DOI：
10.1172/jci39901
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发表时间：
2010-01-01
影响因子：
15.9
通讯作者：
Kousteni, Stavroula
中科院分区：
文献类型：
--
作者：
Rached, Marie-Therese;Kode, Aruna;Kousteni, Stavroula
最近发现，成骨细胞通过分泌骨钙素来调节葡萄糖代谢。然而，目前尚不清楚这种成骨细胞的功能是如何受到转录调控的。由于FoxO1是一个已知的调节葡萄糖动态平衡的几个关键方面的叉头家族转录因子，我们研究了它在成骨细胞中的表达是否可能有助于其代谢功能。在这里，我们显示了只在成骨细胞中缺乏Foxo1的小鼠的胰岛β细胞增殖、胰岛素分泌和胰岛素敏感性增加。成骨细胞特异性FoxO1缺乏影响代谢动态平衡的能力是由于骨钙素表达增加和ESP表达减少，ESP基因编码一种蛋白质，负责降低骨钙素的生物活性。这些结果表明，成骨细胞中FoxO1的表达有助于FoxO1控制血糖的动态平衡，并确认FoxO1是骨骼作为内分泌器官调节葡萄糖代谢能力的关键调节器。
Osteoblasts have recently been found to play a role in regulating glucose metabolism through secretion of osteocalcin. it is unknown, however, how this osteoblast function is regulated transcriptionally. As FoxO1 is a forkhead family transcription factor known to regulate several key aspects of glucose homeostasis, we investigated whether its expression in osteoblasts may contribute to its metabolic functions. Here we show that mice lacking Foxo1 only in osteoblasts had increased pancreatic beta cell proliferation, insulin secretion, and insulin sensitivity. The ability of osteoblast-specific FoxO1 deficiency to affect metabolic homeostasis was due to increased osteocalcin expression and decreased expression of Esp, a gene that encodes a protein responsible for decreasing the bioactivity of osteocalcin. These results indicate that FoxO1 expression in osteoblasts contributes to FoxO1 control of glucose homeostasis and identify FoxO1 as a key modulator of the ability of the skeleton to function as an endocrine organ regulating glucose metabolism.