Signaling mechanisms of glucose-induced F-actin remodeling in pancreatic islet β cells.
Signaling mechanisms of glucose-induced F-actin remodeling in pancreatic islet β cells.
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DOI：
10.1038/emm.2013.73
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发表时间：
2013-08-23
影响因子：
12.8
通讯作者：
Thurmond, Debbie C.
中科院分区：
文献类型：
--
作者：
Kalwat, Michael A.;Thurmond, Debbie C.
维持全身葡萄糖稳态是生存的关键，并受多个器官和内分泌系统的协调控制。胰岛β细胞在营养刺激下分泌胰岛素，然后胰岛素通过循环促进葡萄糖摄取到对胰岛素敏感的组织，如肝脏、骨骼肌和脂肪。在人类对糖尿病个体的全基因组关联研究中发现的许多基因与β细胞的生存和功能直接相关，这证明了β细胞功能障碍是2型糖尿病发展的核心。因此，研究β细胞以受控方式感知葡萄糖和分泌胰岛素的机制是当前糖尿病研究的主要焦点。特别是，最近发现的丝状肌动蛋白(F-肌动蛋白)在调节β细胞胰岛素释放中的详细作用和重组/重塑的要求已经出现在胰岛功能研究的前沿，但由于技术限制在前几年已经失效。最近在活细胞成像和专业试剂方面的进展表明，局部的F-肌动蛋白重塑是营养刺激的胰岛素分泌正常双相模式的必要条件。这篇综述将对肌动蛋白细胞骨架的作用及其对胰岛素分泌的调节的紧急关注提供历史回顾，导致当今该领域正在进行的前沿研究。
The maintenance of whole-body glucose homeostasis is critical for survival, and is controlled by the coordination of multiple organs and endocrine systems. Pancreatic islet β cells secrete insulin in response to nutrient stimuli, and insulin then travels through the circulation promoting glucose uptake into insulin-responsive tissues such as liver, skeletal muscle and adipose. Many of the genes identified in human genome-wide association studies of diabetic individuals are directly associated with β cell survival and function, giving credence to the idea that β-cell dysfunction is central to the development of type 2 diabetes. As such, investigations into the mechanisms by which β cells sense glucose and secrete insulin in a regulated manner are a major focus of current diabetes research. In particular, recent discoveries of the detailed role and requirements for reorganization/remodeling of filamentous actin (F-actin) in the regulation of insulin release from the β cell have appeared at the forefront of islet function research, having lapsed in prior years due to technical limitations. Recent advances in live-cell imaging and specialized reagents have revealed localized F-actin remodeling to be a requisite for the normal biphasic pattern of nutrient-stimulated insulin secretion. This review will provide an historical look at the emergent focus on the role of the actin cytoskeleton and its regulation of insulin secretion, leading up to the cutting-edge research in progress in the field today.
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