Phenotypic characterization of polygenic type 2 diabetes in TALLYHO/JngJ mice
Phenotypic characterization of polygenic type 2 diabetes in TALLYHO/JngJ mice
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DOI：
10.1677/joe.1.06647
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发表时间：
2006-11-01
影响因子：
4
通讯作者：
Naggert, Jurgen K.
中科院分区：
文献类型：
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作者：
Kim, Jung Han;Stewart, Taryn P.;Naggert, Jurgen K.
TALLYHO/JngJ (TH)品系是新建立的2型糖尿病(T2D)和肥胖症多基因小鼠模型，我们之前报道过该模型在糖尿病明显发病后的一些关键生理特征。在目前的工作中，我们对 TH 进行了全面的表型表征，以便完全表征人类 T2D 和肥胖的这一新的相关模型。我们从 4 周龄开始通过测量体重、葡萄糖耐量以及胰岛素、葡萄糖和甘油三酯的血浆水平来监测肥胖和糖尿病的发展。此外，还检查了胰腺的组织学变化以及比目鱼肌中的葡萄糖摄取和葡萄糖转运蛋白 4 (GLUT4) 含量。与年龄和性别匹配的 C57BL/6J (136) 小鼠相比，雄性和雌性 TH 小鼠在 4 周龄时均明显较重、高瘦素血症和高胰岛素血症，且没有葡萄糖不耐受或高血糖。 TH 小鼠在 16 周的研究期间保持较高的体重。 TH 小鼠的高胰岛素血症随着年龄的增长而恶化，但雌性小鼠的程度较雄性轻。雄性和雌性 TH 小鼠的胰岛均增大。雄性 TH 小鼠在第 8 周时表现出葡萄糖耐量受损，并在第 16 周时变得更加明显。雄性 TH 小鼠的血浆葡萄糖水平随着年龄的增长而持续增加，导致明显的糖尿病，而雌性 TH 小鼠在整个研究过程中血糖保持正常。雄性 TH 小鼠的葡萄糖耐量受损和高血糖伴随着基础状态和胰岛素刺激状态下比目鱼肌中 2-脱氧葡萄糖摄取受损，但 GLUT4 含量没有任何减少。有趣的是，雄性 TH 小鼠在糖尿病前期表现出血浆甘油三酯水平急剧升高，并且在整个研究过程中一直保持这一水平。这些发现表明，肥胖和胰岛素抵抗是 TH 表型的固有部分，并且在雄性 TH 小鼠中，葡萄糖耐受不良在进展为明显糖尿病之前是明显的。
The TALLYHO/JngJ (TH) strain is a newly established, polygenic mouse model for type 2 diabetes (T2D) and obesity, and we have previously reported some key physiological features of this model after the overt onset of diabetes. In the present work, we conducted a comprehensive phenotypic characterization of TH in order to completely characterize this new and relevant model for human T2D and obesity. We monitored the development of obesity and diabetes starting at 4 weeks of age by measuring body weight, glucose tolerance, and plasma levels of insulin, glucose, and triglyceride. Additionally, histological alterations in the pancreas and glucose uptake and glucose transporter 4 (GLUT4) content in soleus muscle were also examined. Compared with age- and sex-matched C57BL/6J (136) mice, both male and female TH mice were significantly heavier, hyperleptinemic, and hyperinsulinemic at 4 weeks of age, without glucose intolerance or hyperglycemia. TH mice maintained higher body weights throughout the study period of 16 weeks. The hyperinsulinemia in TH mice worsened with age, but to a lesser degree in females than in males. Both the male and the female TH mice had enlarged pancreatic islets. Male TH mice showed impaired glucose tolerance at 8 weeks that became more prominent at 16 weeks. Plasma glucose levels continuously increased with age in male TH mice resulting in frank diabetes, while female TH mice remained normoglycemic throughout the study. Impaired glucose tolerance and hyperglycemia in male TH mice were accompanied by impaired 2-deoxyglucose uptake in the soleus muscle at basal and insulin-stimulated states, but without any reduction in GLUT4 content. Interestingly, male TH mice exhibited a drastic elevation in plasma triglyceride levels in the pre-diabetic stage that was maintained throughout the study. These findings suggest that obesity and insulin resistance are an inherent part of the TH phenotype and glucose intolerance is evident preceding progression to overt diabetes in male TH mice.