摘要
能量代谢介导2型糖尿病(T2DM)并发症骨代谢紊乱发生是近来生命医学领域的研究热点。T2DM作为因能量代谢紊乱导致的继发性疾病,其成骨细胞(OB)分化及骨形成被抑制且破骨细胞(OC)分化及骨吸收异常升高,引发骨代谢紊乱。AMP依赖蛋白激酶(AMPK)是能量代谢调节的关键分子,以α亚型研究最多,其N-末端含有一保守丝氨酸(Ser)/苏氨酸(Thr)激酶区,该区域保守Thr-172位点开启后可激活多条途径。并且,腺苷三磷酸(ATP)/腺苷一磷酸(AMP)激活AMPK激酶活性/调节功能域可介导OB和/或OC分化及功能。作为能量代谢稳态关键调节器——AMPK,其表达下调是T2DM发生的病理生理学基础,亦导致其并发症骨质代谢紊乱。运动促进OB分化及骨形成并抑制OC分化及骨吸收,且运动过程中ATP/AMP比值下降会激活AMPK。然而,运动通过AMPK调控T2DM的OB或OC分化及功能发挥的相关研究较少,其调控作用机制有待揭示。为此,本研究拟对AMPK调控T2DM骨代谢紊乱及运动干预此过程的相关研究进行梳理,以期为运动改善T2DM骨代谢提供一定理论基础。
Bone metabolism disorder mediated by energy metabolism in type 2 diabetes(T2DM)is a recent research hotspot.T2DM is a secondary disease caused by energy metabolism disorder,with inhibited osteoblast(OB)differentiation and bone formation and promoted osteoclast(OC)differentiation and bone resorption,Results ing in disorder of bone metabolism.AMP-dependent protein kinase(AMPK),a key molecule of energy metabolism regulation,contains a conserved domain of serine(Ser)/threonine(Thr)kinase at the N-terminus of the alpha subtype.When the conserved Thr-172 site in this region is turned on,multiple signal pathways may be activated.Moreover,ATP/AMP activates the activity or regulates domain in AMPK to mediate OB or OC differentiation and function.Down-regulation of AMPKα,a key regulator of energy metabolism homeostasis,is the pathological basis of T2DM,and leads to complications of bone metabolism disorder.Exercise promotes OB differentiation and bone formation and inhibits OC differentiation and bone resorption.A decrease of ATP/AMP ratio during exercise activates AMPKα.However,few studies exist in the regulation of OB or OC differentiation and function by AMPKαin T2DM.The mechanism remains to reveal.Based on the above,this study is to review the related research on AMPKαregulation of bone metabolism disorder in T2DM and exercise intervention,in order to provide a theoretical basis for the study of exercise to improve bone metabolism in T2DM.
作者
陈祥和
余慧琳
徐帅
杨康
张宪亮
赵仁清
孙开宏
CHEN Xianghe;YU Huilin;XU Shuai;YANG Kang;ZHANG Xianliang;ZHAO Renqing;SUN Kaihong(College of Sport,Yangzhou University,Yangzhou 225127,China;College of Sport,Huaiyin Normal College,Huaian 223001,China;College of Sport,Shandong University,Jinan 250000,China;College of Sport,Yangzhou Professional University,Yangzhou 225127,China)
出处
《中国骨质疏松杂志》
CAS
CSCD
北大核心
2019年第11期1650-1654,1663,共6页
Chinese Journal of Osteoporosis
基金
江苏省高等学校科学研究面上项目(17KJB180017)
关键词
AMPK
运动
2型糖尿病
骨形成
骨吸收
AMPK
exercise
type 2 diabetes
bone formation
bone resorption