Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model  

作　　者：ZOU JiangHuan XIONG XiWen LAI BeiBei SUN Min TU Xin GAO Xiang 

机构地区：[1]MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University

出　　处：《Science China(Life Sciences)》2015年第4期359-367,共9页中国科学（生命科学英文版）

基　　金：supported by National Key Technology Support Program(2011BAI15B02,2012BAI39B01);National Key Basic Research Program of China(2011CB944104)

摘　　要：Bone was reported as a crucial organ for regulating glucose homeostasis. In this study, we found that Phex mutant mice(PUG), a model of human X-linked hypophosphatemic rickets(XLH), displayed metabolic abnormality in addition to abnormal phosphate homeostasis, skeletal deformity and growth retardation. Glucose tolerance was elevated with enhanced insulin sensitivity in PUG, though circulating insulin level decreased. Interestingly, bone mineral density defects and glucose metabolic abnormality were both rescued by adding phosphorus- and calcium-enriched supplements in daily diet. Serum insulin level, glucose tolerance and insulin sensitivity showed no differences between PUG and wild-type mice with rescued osteocalcin(OCN) following treatment. Our study suggested that OCN is a potential mediator between mineral homeostasis and glucose metabolism. This investigation brings a new perspective on glucose metabolism regulation through skeleton triggered mineral homeostasis and provides new clues in clinical therapeutics of potential metabolic disorders in XLH patients.Bone was reported as a crucial organ for regulating glucose homeostasis. In this study, we found that Phex mutant mice （PUG）, a model of human X-linked hypophosphatemic rickets （XLH）, displayed metabolic abnormality in addition to abnormal phosphate homeostasis, skeletal deformity and growth retardation. Glucose tolerance was elevated with enhanced insulin sensitivity in PUG, though circulating insulin level decreased. Interestingly, bone mineral density defects and glucose metabolic abnormality were both rescued by adding phosphorus- and calcium-enriched supplements in daily diet. Serum insulin level, glucose tolerance and insulin sensitivity showed no differences between PUG and wild-type mice with rescued osteocalcin （OCN） following treatment. Our study suggested that OCN is a potential mediator between mineral homeostasis and glucose metabolism. This investigation brings a new perspective on glucose metabolism regulation through skeleton triggered mineral homeostasis and provides new clues in clinical therapeutics of potential metabolic disorders in XLH patients.

关 键 词：glucose metabolism mineral homeostasis bone PHEX X-linked hypophosphatemic rickets 

分 类 号：R587.1[医药卫生—内分泌] R681[医药卫生—内科学]