Minireview: The role of the autonomic nervous system in mediating the glucagon response to hypoglycemia.
Minireview: The role of the autonomic nervous system in mediating the glucagon response to hypoglycemia.
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DOI：
10.1210/en.2011-2040
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发表时间：
2012-02
期刊：
影响因子：
4.8
通讯作者：
G. Taborsky;T. Mundinger
中科院分区：
文献类型：
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作者：
G. Taborsky;T. Mundinger
在1型糖尿病中，胰高血糖素对低血糖反应的损害增加了其严重性和持续时间。在非糖尿病个体中，低血糖激活自主神经系统，自主神经系统反过来介导大部分胰高血糖素对中度和显著低血糖的反应。因此，本文的第一个目标是说明和记录这些自主机制。具体来说，我们描述了激活三个自主输入胰岛（副交感神经，交感神经和肾上腺髓质肾上腺素）的低血糖阈值和它们的激活幅度葡萄糖福尔斯从正常下降到接近致命的水平。这意味着它们对胰高血糖素反应的相对贡献取决于低血糖的严重程度。本小综述的第二个目标是讨论糖尿病中已知和可疑的下调或损害这些机制。我们解决中枢神经系统，周围神经系统和胰岛本身的缺陷。它们被分类为由葡萄糖失调引起的功能缺陷或由胰岛的自身免疫攻击引起的结构缺陷。在小评论的最后一部分，我们概述了扭转这些缺陷的方法。这种逆转具有科学和临床益处。科学上，人们可以确定这些缺陷对1型糖尿病早期胰高血糖素反应受损的贡献。在临床上，恢复这种胰高血糖素反应将允许更积极地治疗慢性高血糖症，慢性高血糖症与这种疾病的长期并发症有关。
In type 1 diabetes, the impairment of the glucagon response to hypoglycemia increases both its severity and duration. In nondiabetic individuals, hypoglycemia activates the autonomic nervous system, which in turn mediates the majority of the glucagon response to moderate and marked hypoglycemia. The first goal of this minireview is therefore to illustrate and document these autonomic mechanisms. Specifically we describe the hypoglycemic thresholds for activating the three autonomic inputs to the islet (parasympathetic nerves, sympathetic nerves, and adrenal medullary epinephrine) and their magnitudes of activation as glucose falls from euglycemia to near fatal levels. The implication is that their relative contributions to this glucagon response depend on the severity of hypoglycemia. The second goal of this minireview is to discuss known and suspected down-regulation or damage to these mechanisms in diabetes. We address defects in the central nervous system, the peripheral nervous system, and in the islet itself. They are categorized as either functional defects caused by glucose dysregulation or structural defects caused by the autoimmune attack of the islet. In the last section of the minireview, we outline approaches for reversing these defects. Such reversal has both scientific and clinical benefit. Scientifically, one could determine the contribution of these defects to the impairment of glucagon response seen early in type 1 diabetes. Clinically, restoring this glucagon response would allow more aggressive treatment of the chronic hyperglycemia that is linked to the debilitating long-term complications of this disease.