The search for the mechanism of early sympathetic islet neuropathy in autoimmune diabetes.
The search for the mechanism of early sympathetic islet neuropathy in autoimmune diabetes.
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DOI：
10.1111/dom.12341
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Mundinger TO
中科院分区：
文献类型：
--
作者：
Taborsky GJ Jr;Mei Q;Hackney DJ;Mundinger TO
本文就自身免疫性糖尿病胰岛交感神经早期缺失的机制作一综述。由于我们以前的工作已经证明了低血糖期间胰高血糖素分泌的自主刺激的重要性，这些神经的丧失可能有助于人类1型糖尿病早期这种特异性胰高血糖素反应的已知损害。因此，我们简要回顾自主神经激活，特别是交感神经激活，使随后的胰高血糖素对低血糖的反应的贡献。我们还详细的证据表明，动物模型的自身免疫性糖尿病模拟胰岛交感神经和受损的胰高血糖素反应在人类1型糖尿病中看到的早期损失。利用这些动物模型的数据，我们研究了胰岛神经丢失可能发生的机制。我们提供的证据表明，这不是由于糖尿病高血糖症，但它是有关的淋巴细胞浸润的胰岛。激活存在于交感神经轴突上的p75神经营养因子受体，可以预防eSIN，但有趣的是，不能预防糖尿病。因此，我们似乎已经将免疫相关的胰岛交感神经丧失与免疫介导的胰岛β细胞破坏分开。最后，我们推测一种方法来恢复胰岛的交感神经支配。
This review outlines our search for the mechanism causing the early loss of islet sympathetic nerves in autoimmune diabetes. Since our previous work has documented the importance of autonomic stimulation of glucagon secretion during hypoglycaemia, the loss of these nerves may contribute to the known impairment of this specific glucagon response early in human type 1 diabetes. We therefore briefly review the contribution that autonomic activation, and sympathetic neural activation in particular, makes to the subsequent glucagon response to hypoglycaemia. We also detail evidence that animal models of autoimmune diabetes mimic both the early loss of islet sympathetic nerves and the impaired glucagon response seen in human type 1 diabetes. Using data from these animal models, we examine mechanisms by which this loss of islet nerves could occur. We provide evidence that it is not due to diabetic hyperglycaemia, but it is related to the lymphocytic infiltration of the islet. Ablating the p75 neurotrophin receptor, which is present on sympathetic axons, prevents eSIN, but, interestingly, not diabetes. Thus, we appear to have separated the immune-related loss of islet sympathetic nerves from the immune-mediated destruction of islet β-cells. Finally, we speculate on a way to restore the sympathetic innervation of the islet.
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