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首页> 外文期刊>Journal of cellular physiology. >Osteoblast-specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase-1 engenders insulin resistance in high-fat diet fed mice
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Osteoblast-specific deficiency of ectonucleotide pyrophosphatase or phosphodiesterase-1 engenders insulin resistance in high-fat diet fed mice

机译：Osteoblast-specific ectonucleotide不足焦磷酸酶或phosphodiesterase-1产生在高脂肪饮食喂养小鼠胰岛素抵抗

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摘要

Supraphysiological levels of the osteoblast-enriched mineralization regulator ectonucleotide pyrophosphatase or phosphodiesterase-1 (NPP1) is associated with type 2 diabetes mellitus. We determined the impact of osteoblast-specific Enpp1 ablation on skeletal structure and metabolic phenotype in mice. Female, but not male, 6-week-old mice lacking osteoblast NPP1 expression (osteoblast-specific knockout [KO]) exhibited increased femoral bone volume or total volume (17.50% vs. 11.67%; p < .01), and reduced trabecular spacing (0.187 vs. 0.157 mm; p< .01) compared with floxed (control) mice. Furthermore, an enhanced ability of isolated osteoblasts from the osteoblast-specific KO to calcify their matrix in vitro compared to fl/fl osteoblasts was observed (p<.05). Male osteoblast-specific KO and fl/fl mice showed comparable glucose and insulin tolerance despite increased levels of insulin-sensitizing under-carboxylated osteocalcin (195% increase; p<.05). However, following high-fat-diet challenge, osteoblast-specific KO mice showed impaired glucose and insulin tolerance compared with fl/fl mice. These data highlight a crucial local role for osteoblast NPP1 in skeletal development and a secondary metabolic impact that predominantly maintains insulin sensitivity.
机译：Supraphysiological的水平osteoblast-enriched矿化监管机构ectonucleotide焦磷酸酶或phosphodiesterase-1 (NPP1)有关2型糖尿病。影响osteoblast-specific Enpp1消融骨骼结构和代谢表型老鼠。缺乏成骨细胞NPP1表达式(osteoblast-specific淘汰赛(KO))展出增加股骨骨体积和总量(17.50%比11.67%;小梁间距(0.187 vs 0.157毫米;相比之下,液氧(控制)的老鼠。一个增强的孤立的成骨细胞的能力osteoblast-specific KO钙化他们矩阵比fl / fl成骨细胞在体外观察(p < . 05)。fl / fl老鼠显示类似的葡萄糖和胰岛素宽容,尽管水平的提高insulin-sensitizing under-carboxylated骨钙素(增加195%;雌性的挑战后,osteoblast-specific KO小鼠受损葡萄糖和胰岛素耐受性与fl / fl老鼠。对成骨细胞NPP1骨骼发展主要次生代谢影响维护胰岛素敏感性。

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