Islet loss and alpha cell expansion in type 1 diabetes induced by multiple low-dose streptozotocin administration in mice
Islet loss and alpha cell expansion in type 1 diabetes induced by multiple low-dose streptozotocin administration in mice
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DOI：
10.1677/joe.0.1650093
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发表时间：
2000-04-01
影响因子：
4
通讯作者：
Sandler, S
中科院分区：
文献类型：
--
作者：
Li, Z;Karlsson, FA;Sandler, S
本研究的目的是研究小鼠多次低剂量链脲佐菌素后1型糖尿病发展过程中的α细胞群。为此，C57BL/Ks雄性小鼠注射链脲佐菌素（40 mg/kg体重）5天。在28天内监测高血糖的发展，并对胰岛内分泌细胞进行形态计量学分析。两次注射链脲佐菌素后观察到胰岛细胞面积减少。在整个研究期间，该区域随后平均减少35%。胰岛素阳性的β细胞逐渐从确定的胰岛中消失。从第7天开始出现高血糖，与高血糖同时发生胰岛素炎。对每个胰岛面积的α细胞数量的分析显示，该细胞群增加了2至3倍，在第21天达到最高值。共聚焦显微镜分析显示，ICA 512蛋白酪氨酸磷酸酶在第21天的α细胞中强烈表达，表明糖尿病状态下具有较高的分泌活性。由此可见，多次低剂量链脲佐菌素治疗C57BL/Ks雄性小鼠可导致部分朗格汉斯胰岛消失。在剩余的胰岛组织中发生α细胞的扩增，反映了胰岛内β细胞的损失以及α细胞的再生。
The aim of this study was to investigate the alpha cell population during the development of type 1 diabetes following multiple low-dose streptozotocin administration in mice. For this purpose C57BL/Ks male mice were injected with streptozotocin (40 mg/kg body weight for 5 days). Development of hyperglycemia was monitored over 28 days and a morphometric analysis of islet endocrine cells was performed. A reduction of islet cell area was observed after two injections of streptozotocin. The subsequent decrease of the area throughout the study period averaged 35%. Insulin-positive beta cells gradually disappeared from the identified islets. Hyperglycemia was present from day 7 onwards and in parallel with hyper-glycemia, insulitis developed. An analysis of the alpha cell number per islet area revealed a 2- to 3-fold increase in this cell population, with the highest value on day 21. Confocal microscopy analysis of the ICA 512 protein tyrosine phosphatase revealed strong expression in the alpha cells at day 21, suggesting high secretory activity in the diabetic state. It is concluded that multiple low-dose streptozotocin treatment of C57BL/Ks male mice causes the disappearance of a fraction of the islets of Langerhans. In the remaining islet tissue an expansion of alpha cells occurs, reflecting a loss of intraislet beta cells as well as a regeneration of alpha cells.