Limb regeneration is impaired in an adult zebrafish model of diabetes mellitus.
Limb regeneration is impaired in an adult zebrafish model of diabetes mellitus.
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DOI：
10.1111/j.1524-475x.2010.00613.x
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Intine RV
中科院分区：
文献类型：
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作者：
Olsen AS;Sarras MP Jr;Intine RV
斑马鱼（Danio Rerio）是研究发育过程、人类疾病和组织再生的模式生物。我们报告说，肢体再生严重受损，在我们新开发的成年斑马鱼模型的I型糖尿病。腹腔注射链脲佐菌素的成年野生型斑马鱼导致持续的高血糖状态，如通过升高的空腹血糖值和增加的血清蛋白糖化所确定的。血清胰岛素水平也降低，胰腺组织化学显示高血糖鱼中胰岛素信号量较少。此外，糖尿病并发症的视网膜变薄和肾小球基底膜增厚（早期迹象视网膜病变和肾病）导致的高血糖状态是明显的链脲佐菌素注射鱼在三周。最重要的是，肢体再生，尾鳍截肢后，是严重受损的糖尿病斑马鱼。未发现胰腺外的非特异性毒性作用导致肢体再生受损。这个使用成年斑马鱼的实验系统促进了广泛的遗传和分子方法来研究糖尿病背景下的再生。
The zebrafish (Danio Rerio) is an established model organism for the study of developmental processes, human disease and tissue regeneration. We report that limb regeneration is severely impaired in our newly developed adult zebrafish model of type I diabetes. Intraperitoneal streptozocin injection of adult, wild type zebrafish results in a sustained hyperglycemic state as determined by elevated fasting blood glucose values and increased glycation of serum protein. Serum insulin levels are also decreased and pancreas immunohistochemisty revealed a lesser amount of insulin signal in hyperglycemic fish. Additionally, the diabetic complications of retinal thinning and glomerular basement membrane thickening (early signs of retinopathy and nephropathy) resulting from the hyperglycemic state were evident in streptozocin injected fish at three weeks. Most significantly, limb regeneration, following caudal fin amputation, is severely impaired in diabetic zebrafish. Nonspecific toxic effects outside the pancreas were not found to contribute to impaired limb regeneration. This experimental system using adult zebrafish facilitates a broad spectrum of genetic and molecular approaches to study regeneration in the diabetic background.