Institute of Bone injury of Traditional Chinese Medicine, Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
Institute of Bone injury of Traditional Chinese Medicine, Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Age-related Diseases, Medical College, Yangzhou University, Yangzhou 225001, China.
Exp Gerontol. 2018 Nov;113:106-112. doi: 10.1016/j.exger.2018.09.027. Epub 2018 Oct 4.
Age is a major risk factor for developing chronic diseases, including type 2 diabetes and osteoporosis. Emerging evidences suggest that the disorder of bone metabolism in osteoporosis is involved in the pathogenesis of glucose intolerance, insulin resistance and type 2 diabetes. However, their etiology and relative regulatory factors still remain elusive to clinicians and researchers. In this study, rats were divided into two groups: normal sham surgery control and ovariectomized (OVX) groups. We evaluated the global bone parameters, glucose metabolism, protein and gene expressions in both skeletal muscle and adipocytes. The present findings showed that the bone mineral density (BMD) and compression load of bone were markedly reduced in OVX rats as revealed by micro-CT, dual energy X-ray absorptiometry and bone biomechanics analysis. Besides, plasma estrogen, total alkaline phosphatase (TALP) and osteocalcin levels were significantly decreased in the OVX rats, but body weight, fat mass and plasma tartrate-resistant acid phosphatase (TRAP) and chemerin levels were significantly increased in the OVX rats. More interestingly, we found that p-AKT, p-P38MAPK, glucose transporter 4 (GLUT4) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) contents as well as GLUT4 and PGC-1α mRNA expression were significantly decreased in skeletal muscle and adipocytes of OVX rats. In conclusion, our results indicated that whole-body glucose metabolism and glucose intolerance in OVX rats was degressive, suggesting there was a novel link between osteoporosis and whole body glucose homeostasis, which are controlled by the P38MAPK/PGC-1α/GLUT4 signaling pathway.
年龄是导致慢性疾病（包括 2 型糖尿病和骨质疏松症）发生的主要危险因素。新出现的证据表明，骨质疏松症中骨代谢的紊乱与葡萄糖耐量受损、胰岛素抵抗和 2 型糖尿病的发病机制有关。然而，其病因和相对调节因素对临床医生和研究人员来说仍然难以捉摸。在这项研究中，将大鼠分为两组：正常假手术对照组和卵巢切除（OVX）组。我们评估了两组大鼠的整体骨参数、葡萄糖代谢、骨骼肌和脂肪细胞中的蛋白质和基因表达。本研究发现，骨矿物质密度（BMD）和骨压缩载荷在 OVX 大鼠中明显降低，这一点通过微 CT、双能 X 射线吸收仪和骨生物力学分析得到了证实。此外，OVX 大鼠的血浆雌激素、总碱性磷酸酶（TALP）和骨钙素水平显著降低，而体重、脂肪量和血浆抗酒石酸酸性磷酸酶（TRAP）和 chemerin 水平显著升高。更有趣的是，我们发现 OVX 大鼠骨骼肌和脂肪细胞中的 p-AKT、p-P38MAPK、葡萄糖转运蛋白 4（GLUT4）和过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α）含量以及 GLUT4 和 PGC-1αmRNA 表达均显著降低。综上所述，我们的结果表明，OVX 大鼠的全身葡萄糖代谢和葡萄糖耐量下降，提示骨质疏松症与全身葡萄糖稳态之间存在新的联系，这种联系受 P38MAPK/PGC-1α/GLUT4 信号通路的控制。
