Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models
Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models
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DOI：
10.1152/ajpendo.90937.2008
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发表时间：
2009-04-01
影响因子：
5.1
通讯作者：
Burr, David B.
中科院分区：
文献类型：
--
作者：
Reinwald, Susan;Peterson, Richard G.;Burr, David B.
莱因瓦尔德·S，彼得森RG，艾伦先生，伯尔·DB。ZDF和ZDSD啮齿动物模型中与2型糖尿病发病相关的骨骼变化。AM J生理学内分泌代谢酶296：E765-E774,2009。在美国，2型糖尿病(T2D)的发病率和流行率继续以前所未有的速度上升，特别是在肥胖率较高的人群中。由于这种疾病的复杂性和异质性，T2D对骨量、几何形状、结构、强度和抗折性的影响尚未得到无可争辩的表征。这项研究使用常用的Zucker糖尿病脂肪(ZDF)和Zucker糖尿病Spraogue-Dawley(ZDSD)品系的骨骼成熟雄性糖尿病大鼠作为替代模型，以评估可归因于T2D样状态的骨骼变化。动物被安乐死后，采用双能X线骨密度仪、外周定量断层扫描和显微CT成像方法，通过三点弯曲或压缩力学测试方法收集骨数据。ZDF和ZDSD糖尿病大鼠表现出较低的骨密度，这与单调负荷下股骨中段和L-4椎体的结构强度下降和脆性增加相一致。在两种糖尿病啮齿动物品系中，脊椎小梁形态都受到损害，而ZDSD糖尿病大鼠在脊柱处表现出额外的骨材料特性的表型损害。由于在ZDSD大鼠品系中出现的类T2D状态的代谢起源与成人起病糖尿病高度相关，因此它是未来临床前研究的一个特别有吸引力的新模型。
Reinwald S, Peterson RG, Allen MR, Burr DB. Skeletal changes associated with the onset of type 2 diabetes in the ZDF and ZDSD rodent models. Am J Physiol Endocrinol Metab 296: E765-E774, 2009. First published January 21, 2009; doi:10.1152/ajpendo.90937.2008.The incidence and prevalence of type 2 diabetes (T2D) continue to escalate at an unprecedented rate in the United States, particularly among populations with high rates of obesity. The impact of T2D on bone mass, geometry, architecture, strength, and resistance to fracture has yet to be incontrovertibly characterized because of the complex and heterogeneous nature of this disease. This study utilized skeletally mature male diabetic rats of the commonly used Zucker diabetic fatty (ZDF) and Zucker diabetic Sprague-Dawley (ZDSD) strains as surrogate models to assess alterations in bone attributable to T2D-like states. After the animals were euthanized, bone data were collected using dual-energy X-ray absorptiometry, peripheral quantitative tomography, and micro-CT imaging modalities and via three-point bending or compression mechanical testing methods. ZDF and ZDSD diabetic rats exhibited lower bone mineral densities, which coincided with declines in structural strength and increased fragility at the femoral midshaft and the L-4 vertebral body in response to monotonic loading. Vertebral trabecular morphology was compromised in both diabetic rodent strains, and ZDSD diabetic rats exhibited additional phenotypic impairments to bone material properties at the spine. Because the metabolic origin of the T2D-like state that develops in the ZDSD rat strain is highly relevant to adult-onset diabetes, it is a particularly attractive novel model for future preclinical research.