...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Endocrinology >Impaired Musculoskeletal Response to Age and Exercise in PPAR beta(-/-) Diabetic Mice
【24h】

Impaired Musculoskeletal Response to Age and Exercise in PPAR beta(-/-) Diabetic Mice

机译：PPAR beta（-/-）糖尿病小鼠对年龄和运动的肌肉骨骼反应受损

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Fragility fractures are recognized complication of diabetes, but yet the underlying mechanisms remain poorly understood. This is particularly pronounced in type 2 diabetes in which the propensity to fall is increased but bone mass is not necessarily low. Thus, whether factors implicated in the development of insulin resistance and diabetes directly impact on the musculoskeletal system remains to be investigated. PPAR beta(-/-) mice have reduced metabolic activity and are glucose intolerant. We examined changes in bone and muscle in PPAR beta(-/-) mice and investigated both the mechanism behind those changes with age as well as their response to exercise. Compared with their wild type, PPAR beta(-/-) mice had an accelerated and parallel decline in both muscle and bone strength with age. These changes were accompanied by increased myostatin expression, low bone formation, and increased resorption. In addition, mesenchymal cells from PPAR beta(-/-) had a reduced proliferation capacity and appeared to differentiate into more of an adipogenic phenotype. Concomitantly we observed an increased expression of PPAR beta, characteristic of adipocytes. The anabolic responses of muscle and bone to exercise were also diminished in PPAR beta(-/-) mice. The periosteal bone formation response to direct bone compression was, however, maintained, indicating that PPAR beta controls periosteal bone formation through muscle contraction and/or metabolism. Taken together, these data indicate that PPAR beta deficiency leads to glucose intolerance, decreased muscle function, and reduced bone strength. On a molecular level, PPAR beta appears to regulate myostatin and PPAR beta expression in muscle and bone, thereby providing potential new targets to reverse bone fragility in patients with metabolic disturbances.
机译：易碎性骨折是公认的糖尿病并发症，但其潜在机制仍知之甚少。这在2型糖尿病中尤其明显，在2型糖尿病中，跌倒的倾向增加了，但骨量不一定很低。因此，涉及胰岛素抵抗和糖尿病发展的因素是否直接影响肌肉骨骼系统尚待研究。 PPAR beta（-/-）小鼠的代谢活性降低，并且不耐葡萄糖。我们检查了PPAR beta（-/-）小鼠骨骼和肌肉的变化，并研究了这些变化随年龄增长的机制以及它们对运动的反应。与野生型相比，PPAR beta（-/-）小鼠的肌肉和骨骼强度随着年龄的增长而加速并平行下降。这些变化伴随着肌肉生长抑制素表达的增加，低骨形成和吸收的增加。此外，来自PPAR beta（-/-）的间充质细胞的增殖能力降低，并且似乎分化为更多的脂肪形成表型。同时，我们观察到脂肪细胞特征性的PPARβ表达增加。在PPAR beta（-/-）小鼠中，肌肉和骨骼对运动的合成代谢反应也有所减少。然而，维持了对直接骨压缩的骨膜骨形成反应，表明PPARβ通过肌肉收缩和/或代谢控制骨膜骨形成。综上所述，这些数据表明PPARβ缺乏会导致葡萄糖耐受不良，肌肉功能下降和骨骼强度下降。在分子水平上，PPARβ似乎可以调节肌肉和骨骼中的肌肉生长抑制素和PPARβ的表达，从而提供潜在的新靶点来逆转代谢紊乱患者的骨脆性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号