CMHX008,a PPAR γ partial agonist,enhances insulin sensitivity with minor influences on bone loss
作者机构：Department of EndocrinologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China College of PharmacyChongqing Medical UniversityChina The Chongqing Key Laboratory of Translational Medicine in Major Metabolic DiseasesThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China Department of Nutrition and Food HygieneSchool of Public Health and ManagementChongqing Medical UniversityChongqing400016China Canada-China-New Zealand Joint Laboratory of Maternal and Fetal MedicineChongqing Medical UniversityChongqing400016China Department of Nutrition and Food ScienceTexas A&M UniversityCollege StationTX77843USA
出 版 物：《Genes & Diseases》 (基因与疾病（英文）)
年 卷 期：2018年第5卷第3期
页 面：290-299页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：supported by the National Natural Science Foundation of China(81270947 and 81570763,to XX) the National Program on Key Basic Research Project of China(973 Program,2012CB517505,to XX) the Fundamental Science and Advanced Technology Research of Chongqing(Major Project,CSTC2015jcyjB0146) Chongqing Graduate Student Research Innovation Fund(CYB15095,to HY)
主 题：Osteoblasts Peroxisome proliferator-activated receptor g Thiazolidinediones TR-FRET Type 2 diabetes mellitus
摘 要：Traditional thiazolidinediones(TZDs),such as rosiglitazone,are peroxisome proliferator-activated receptor g(PPARg)potent agonists that can be used to treat type 2 diabetes but carry unwanted effects,including increased risk for *** present work aimed to compare the insulin-sensitizing efficacies and bone-loss side effects of CMHX008,a novel TZDs-like PPARg partial agonist,with those of rosiglitazone.A TR-FRET PPARg competitive binding assay was used to compare the binding affinity between CMHX008 and *** were administered vehicle,CMHX008 or rosiglitazone for 16 *** stem cells(MSCs)were used to examine differences in differentiation into osteoblasts after compounds ***-FRET showed lower affinity to PPARg by CMHX008 compared with *** treated with CMHX008 showed insulin sensitization similar to that of mice treated with rosiglitazone,which was related to the significant inhibition of PPARg Ser273 phosphorylation and improved insulin sensitivity by facilitating the phosphorylation of insulin receptor and Akt in adipose ***-CT and histomorphometric analyses demonstrated that the degree of trabecular bone loss after treatment with CMHX008 was weaker than that observed with rosiglitazone,as evidenced by consistent changes in BV/TV,Tb.N,***,***,and the mineral apposition *** treated with CMHX008 showed higher ALP activity and mRNA levels of bone formation markers than did cells treated with rosiglitazone in the osteoblast differentiation ***,CMHX008 showed insulin-sensitizing effects similar to those of rosiglitazone with a lower risk of bone loss,suggesting that PPARg sparing eliminates the skeletal side effects of TZDs while maintaining their insulin-sensitizing properties.
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