Glucose control of glucagon secretion-'There's a brand-new gimmick every year'.
Glucose control of glucagon secretion-'There's a brand-new gimmick every year'.
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DOI：
10.3109/03009734.2016.1154905
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发表时间：
2016-05
影响因子：
3.4
通讯作者：
Gylfe E
中科院分区：
文献类型：
--
作者：
Gylfe E
来自胰腺α细胞的胰高血糖素是一种主要的血糖调节激素，其最重要的作用是预防低血糖，由于大脑强烈依赖葡萄糖作为能源，低血糖可能危及生命。胰腺β细胞功能障碍或自身免疫性破坏后缺乏降血糖胰岛素是公认的糖尿病原因，但最近的证据表明，除非胰岛素缺乏伴有胰高血糖素分泌过多，否则不会发生糖尿病性高血糖症。因此，胰高血糖素释放已成为糖尿病管理中越来越重要的目标。尽管经过数十年的研究，对胰高血糖素分泌如何调节的理解仍然难以捉摸，并且继续提出根本不同的机制。自主神经系统是胰高血糖素释放的重要决定因素，但很明显，分泌也在胰岛内直接调节。本文综述了葡萄糖调节胰高血糖素释放的胰岛机制。我们认为，α-细胞内源性过程对低血糖恢复期间胰高血糖素释放的调节最为重要，δ-细胞生长抑素的旁分泌抑制作用形成了高血糖症时胰高血糖素的脉冲式释放。电偶联的β细胞通过释放影响α细胞和δ细胞的同步因子最终决定胰岛激素的脉动性。
Glucagon from the pancreatic α-cells is a major blood glucose-regulating hormone whose most important role is to prevent hypoglycaemia that can be life-threatening due to the brain’s strong dependence on glucose as energy source. Lack of blood glucose-lowering insulin after malfunction or autoimmune destruction of the pancreatic β-cells is the recognized cause of diabetes, but recent evidence indicates that diabetic hyperglycaemia would not develop unless lack of insulin was accompanied by hypersecretion of glucagon. Glucagon release has therefore become an increasingly important target in diabetes management. Despite decades of research, an understanding of how glucagon secretion is regulated remains elusive, and fundamentally different mechanisms continue to be proposed. The autonomous nervous system is an important determinant of glucagon release, but it is clear that secretion is also directly regulated within the pancreatic islets. The present review focuses on pancreatic islet mechanisms involved in glucose regulation of glucagon release. It will be argued that α-cell-intrinsic processes are most important for regulation of glucagon release during recovery from hypoglycaemia and that paracrine inhibition by somatostatin from the δ-cells shapes pulsatile glucagon release in hyperglycaemia. The electrically coupled β-cells ultimately determine islet hormone pulsatility by releasing synchronizing factors that affect the α- and δ-cells.