Diabetic pdx1-mutant zebrafish show conserved responses to nutrient overload and anti-glycemic treatment.
Diabetic pdx1-mutant zebrafish show conserved responses to nutrient overload and anti-glycemic treatment.
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DOI：
10.1038/srep14241
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发表时间：
2015-09-18
影响因子：
4.6
通讯作者：
Meyer D
中科院分区：
文献类型：
--
作者：
Kimmel RA;Dobler S;Schmitner N;Walsen T;Freudenblum J;Meyer D
糖尿病的特征在于由于产生胰岛素的β细胞的损失或功能障碍而破坏葡萄糖稳态。在这项工作中，我们表征了斑马鱼pdx 1突变体的胰岛发育和功能，pdx 1是一种与人类糖尿病遗传形式有关的基因，与2型糖尿病易感性增加有关。Pdx1突变斑马鱼具有减少的β细胞、减少的胰岛素和升高的葡萄糖的关键糖尿病特征。高血糖症对药物抗糖尿病治疗有反应，并且正如在哺乳动物糖尿病模型中经常看到的那样，pdx1突变体的β细胞显示出对营养过载的敏感性。这种独特的糖尿病遗传模型为阐明高血糖病理学背后的机制提供了新的工具，并将允许在适合高通量方法的模型生物体中测试新型治疗干预措施。
Diabetes mellitus is characterized by disrupted glucose homeostasis due to loss or dysfunction of insulin-producing beta cells. In this work, we characterize pancreatic islet development and function in zebrafish mutant for pdx1, a gene which in humans is linked to genetic forms of diabetes and is associated with increased susceptibility to Type 2 diabetes. Pdx1 mutant zebrafish have the key diabetic features of reduced beta cells, decreased insulin and elevated glucose. The hyperglycemia responds to pharmacologic anti-diabetic treatment and, as often seen in mammalian diabetes models, beta cells of pdx1 mutants show sensitivity to nutrient overload. This unique genetic model of diabetes provides a new tool for elucidating the mechanisms behind hyperglycemic pathologies and will allow the testing of novel therapeutic interventions in a model organism that is amenable to high-throughput approaches.