Insulin secretion in health and disease: genomics, proteomics and single vesicle dynamics
Insulin secretion in health and disease: genomics, proteomics and single vesicle dynamics
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DOI：
10.1042/bst0340247
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发表时间：
2006-04-01
影响因子：
3.9
通讯作者：
Ravier, M
中科院分区：
文献类型：
--
作者：
Rutter, GA;Varadi, A;Ravier, M
胰岛β细胞的胰岛素分泌缺陷是II型（非胰岛素依赖型）糖尿病的一种常见情况。使用全内反射荧光显微镜实现的单个胞吐事件的纳米力学的数字成像分析使我们能够证明胰岛素通过瞬时或“腔捕获”事件释放，由此囊泡和质膜瞬时和可逆地融合。这些研究揭示，在II型糖尿病的体外模型中，失败融合事件的数量增加导致胰岛素分泌缺陷。在mRNA和蛋白质水平上对β细胞基因表达的全基因组变化进行补充分析，现在有助于鉴定其表达改变可能导致糖尿病β细胞分泌缺陷的关键分子。
Defective insulin secretion from pancreatic islet beta-cells is a sine quo non of Type II (non-insulin-dependent) diabetes. Digital imaging analysis of the nanomechanics of individual exocytotic events, achieved using total internal reflection fluorescence microscopy, has allowed us to demonstrate that insulin is released via transient or 'cavicapture' events whereby the vesicle and plasma membranes fuse transiently and reversibly. Such studies reveal that an increase in the number of abortive fusion events contributes to defective insulin secretion in in vitro models of Type II diabetes. Complementary analyses of genome-wide changes in beta-cell gene expression, at both the mRNA and protein levels, are now facilitating the identification of key molecular players whose altered expression may contribute to the secretory defects in the diabetic beta-cell.