肌醇对2型糖尿病db/db小鼠骨量减少及代谢紊乱的干预作用及其机制

项目名称： 肌醇对2型糖尿病db/db小鼠骨量减少及代谢紊乱的干预作用及其机制

项目编号： No.81200644

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 戴志洁

作者单位： 中南大学

项目金额： 23万元

中文摘要： 2型糖尿病患者的骨量减少及代谢紊乱问题日益受到人们关注，人们试图寻找新的有效治疗方案。肌醇，已被证实在小鼠正常骨形成及发育中起着关键作用，并可有效预防绝经后妇女的骨质流失；此外，还可有效调节多囊卵巢综合症患者及合并代谢综合征的绝经后妇女的代谢紊乱情况。然而，迄今为止，尚无肌醇干预2型糖尿病及其合并症的任何报道。本课题拟以2型糖尿病db/db小鼠为动物模型，探讨：1）肌醇对2型糖尿病db/db小鼠骨密度减低、骨微结构不良及骨更新率的影响，以及其机制是否在于调节小鼠骨髓间质干细胞的增殖及其向成骨细胞或脂肪细胞的分化成熟；2）肌醇对2型糖尿病db/db小鼠高血糖、高血脂、肥胖、高胰岛素血症及胰岛素抵抗的改善作用，以及是否通过I(1,4,5)P3- Ca2+ 信号通路来影响胰岛素分泌。本课题将为肌醇在2型糖尿病及其合并症治疗中的应用提供理论依据。

中文关键词： 肌醇；2型糖尿病；骨量减少；代谢紊乱；db/db小鼠

英文摘要： Osteopenia and metabolic syndrome in patients with type 2 diabetes mellitus (T2DM) are getting more and more attention, with an urgent need for new effective and targeted agents. Myo-inositol, already confirmed to be essential in osteogenesis, bone formation and bone mass determination in mice, has also been proved as a protective factor against osteoporosis in postmenopausal women. Moreover, myo-inositol has been shown to be an effective treatment for metabolic disorders in polycystic ovary syndrome patients or postmenopausal women, such as hyperglycemia, hyperinsulinemia, insulin resistance, obesity and dyslipidemia. Its role in osteopenia and dysmetabolism in T2DM nonetheless is unclear and has never been reported. With the T2DM db/db mice model, this study aims to make clear the effect of myo-inositol against decreased bone mineral density, impaired bone structure and abnormal bone turnover in T2DM. To understand the underlining mechanisms, mesenchymal stem cells will be isolated, and their proliferation and differentiation to osteoblasts or adipocytes will be investigated. Meanwhile, the role of myo-inositol in metabolic disorders of T2DM, such as hyperglycemia, hyperinsulinemia, insulin resistance, obesity and dyslipidemia, will be studied by detecting the relative biochemical indices from serum, urine or

英文关键词： myo-inositol；type 2 diabetes；osteopenia；dysmetabolism；db/db mice