Holz G G, Leech C A, Habener J F
Department of Physiology and Neuroscience, Medical Sciences Building Room 442, New York University School of Medicine, 550 First Avenue, NY New York 10016, USA.
Biochimie. 2000 Sep-Oct;82(9-10):915-26. doi: 10.1016/s0300-9084(00)01171-8.
Cholera toxin, pertussis toxin, mastoparan, maitotoxin, and alpha-latrotoxin are complex protein or polyether-based toxins of bacterial, insect, or phytoplankton origin that act with high potency at the endocrine pancreas to stimulate secretion of insulin from beta-cells located in the islets of Langerhans. The remarkable insulinotropic properties of these toxins have attracted considerable attention by virtue of their use as selective molecular probes for analyses of beta-cell stimulus-secretion coupling. Targets of the toxins include heptahelical cell surface receptors, GTP-binding proteins, ion channels, Ca(2+) stores, and the exocytotic secretory apparatus. Here we review the value of insulinotropic toxins from the perspective of their established use in the study of signal transduction pathways activated by the blood glucose-lowering hormone glucagon-like peptide-1 (GLP-1). Our analysis of one insulinotropic toxin (alpha-latrotoxin) leads us to conclude that there exists a process of molecular mimicry whereby the 'lock and key'analogy inherent to hormone-receptor interactions is reproduced by a toxin related in structure to GLP-1.
霍乱毒素、百日咳毒素、肥大细胞脱粒肽、 maitotoxin和α- latrotoxin是源自细菌、昆虫或浮游植物的复杂蛋白质或基于聚醚的毒素，它们在内分泌胰腺中具有高效活性，可刺激位于胰岛的β细胞分泌胰岛素。这些毒素显著的促胰岛素分泌特性，因其作为分析β细胞刺激-分泌偶联的选择性分子探针而备受关注。毒素的作用靶点包括七螺旋细胞表面受体、GTP结合蛋白、离子通道、Ca(2+)储存库和胞吐分泌装置。在此，我们从其在研究降血糖激素胰高血糖素样肽-1 (GLP-1)激活的信号转导途径中的既定用途角度，综述促胰岛素毒素的价值。我们对一种促胰岛素毒素(α- latrotoxin)的分析得出结论，存在一种分子模拟过程，即与GLP-1结构相关的毒素再现了激素-受体相互作用中固有的“锁和钥匙”类比。
