Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Nat Med. 2011 Jun 19;17(7):888-92. doi: 10.1038/nm.2371.
Acetylcholine is a neurotransmitter that has a major role in the function of the insulin-secreting pancreatic beta cell. Parasympathetic innervation of the endocrine pancreas, the islets of Langerhans, has been shown to provide cholinergic input to the beta cell in several species, but the role of autonomic innervation in human beta cell function is at present unclear. Here we show that, in contrast to the case in mouse islets, cholinergic innervation of human islets is sparse. Instead, we find that the alpha cells of human islets provide paracrine cholinergic input to surrounding endocrine cells. Human alpha cells express the vesicular acetylcholine transporter and release acetylcholine when stimulated with kainate or a lowering in glucose concentration. Acetylcholine secretion by alpha cells in turn sensitizes the beta cell response to increases in glucose concentration. Our results demonstrate that in human islets acetylcholine is a paracrine signal that primes the beta cell to respond optimally to subsequent increases in glucose concentration. Cholinergic signaling within islets represents a potential therapeutic target in diabetes, highlighting the relevance of this advance to future drug development.
乙酰胆碱是一种神经递质，在胰岛素分泌的胰腺β细胞功能中起主要作用。已经证明，胰岛的副交感神经支配提供了几种物种的β细胞胆碱能输入，但自主神经支配在人类β细胞功能中的作用目前尚不清楚。在这里，我们表明，与在小鼠胰岛中的情况相反，人类胰岛中的胆碱能神经支配稀疏。相反，我们发现人类胰岛的α细胞为周围的内分泌细胞提供旁分泌的胆碱能输入。人α细胞表达囊泡乙酰胆碱转运体，当受到海人藻酸或葡萄糖浓度降低的刺激时，释放乙酰胆碱。α细胞分泌的乙酰胆碱反过来使β细胞对葡萄糖浓度升高的反应更加敏感。我们的结果表明，在人类胰岛中，乙酰胆碱是一种旁分泌信号，使β细胞能够对随后的葡萄糖浓度升高做出最佳反应。胰岛内的胆碱能信号代表糖尿病的潜在治疗靶点，突出了这一进展对未来药物开发的相关性。
