Alberta Diabetes Institute, University of Alberta, Edmonton, Canada.
Diabetes Obes Metab. 2012 Oct;14 Suppl 3:143-51. doi: 10.1111/j.1463-1326.2012.01642.x.
Impaired insulin secretion from pancreatic β-cells is a major factor in the pathogenesis of type 2 diabetes. The main regulator of insulin secretion is the plasma glucose concentration. Insulin secretion is modified by other nutrients, circulating hormones and the autonomic nervous system, as well as local paracrine and autocrine signals. Autocrine signalling involves diffusible molecules that bind to receptors on the same cell from which they have been released. The first transmitter to be implicated in the autocrine regulation of β-cell function was insulin itself. The importance of autocrine insulin signalling is underscored by the finding that mice lacking insulin receptors in β-cells are glucose intolerant. In addition to insulin, β-cells secrete a variety of additional substances, including peptides (e.g. amylin, chromogranin A and B and their cleavage products), neurotransmitters (ATP and γ-aminobutyric acid) and ions (e.g. zinc). Here we review the autocrine effects of substances secreted from β-cells, with a focus on acute effects in stimulus-secretion coupling, present some novel data and discuss the general significance of autocrine signals for the regulation of insulin secretion.
胰岛β细胞胰岛素分泌受损是 2 型糖尿病发病机制中的一个主要因素。胰岛素分泌的主要调节因子是血浆葡萄糖浓度。胰岛素分泌还受到其他营养素、循环激素和自主神经系统的调节，以及局部旁分泌和自分泌信号的调节。自分泌信号涉及可扩散分子，这些分子与从其释放的同一细胞上的受体结合。第一个涉及β细胞功能自分泌调节的递质是胰岛素本身。β细胞缺乏胰岛素受体的小鼠表现为葡萄糖不耐受，这凸显了自分泌胰岛素信号的重要性。除了胰岛素，β细胞还分泌多种其他物质，包括肽（如胰淀素、嗜铬粒蛋白 A 和 B 及其裂解产物）、神经递质（ATP 和γ-氨基丁酸）和离子（如锌）。本文综述了β细胞分泌的物质的自分泌作用，重点介绍了在刺激-分泌偶联中的急性作用，提供了一些新的数据，并讨论了自分泌信号对胰岛素分泌调节的一般意义。
