Rorsman P, Berggren P O, Bokvist K, Ericson H, Möhler H, Ostenson C G, Smith P A
Department of Medical Physics, Gothenburg University, Sweden.
Nature. 1989 Sep 21;341(6239):233-6. doi: 10.1038/341233a0.
The endocrine part of the pancreas plays a central role in blood-glucose regulation. It is well established that an elevation of glucose concentration reduces secretion of the hyperglycaemia-associated hormone glucagon from pancreatic alpha 2 cells. The mechanisms involved, however, remain unknown. Electrophysiological studies have demonstrated that alpha 2 cells generate Ca2+-dependent action potentials. The frequency of these action potentials, which increases under conditions that stimulate glucagon release, is not affected by glucose or insulin. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is present in the endocrine part of the pancreas at concentrations comparable to those encountered in the central nervous system, and co-localizes with insulin in pancreatic beta cells. We now describe a mechanism whereby GABA, co-secreted with insulin from beta cells, may mediate part of the inhibitory action of glucose on glucagon secretion by activating GABAA-receptor Cl- channels in alpha 2 cells. These observations provide a model for feedback regulation of glucagon release, which may be of significance for the understanding of the hypersecretion of glucagon frequently associated with diabetes.
胰腺的内分泌部分在血糖调节中起核心作用。葡萄糖浓度升高会降低胰腺α2细胞分泌与高血糖相关的激素胰高血糖素，这一点已得到充分证实。然而，其中涉及的机制仍不清楚。电生理研究表明，α2细胞可产生依赖钙离子的动作电位。这些动作电位的频率在刺激胰高血糖素释放的条件下会增加，但不受葡萄糖或胰岛素的影响。抑制性神经递质γ-氨基丁酸（GABA）在胰腺内分泌部分的浓度与中枢神经系统中的浓度相当，并且在胰腺β细胞中与胰岛素共定位。我们现在描述一种机制，即与胰岛素从β细胞共同分泌的GABA，可能通过激活α2细胞中的GABAA受体氯离子通道，介导葡萄糖对胰高血糖素分泌的部分抑制作用。这些观察结果为胰高血糖素释放的反馈调节提供了一个模型，这可能对理解经常与糖尿病相关的胰高血糖素分泌过多具有重要意义。
