Glucose-stimulated insulin secretion from the islet beta-cell involves a sequence of metabolic events and an interplay between a wide range of signaling pathways leading to the generation of second messengers (e.g., cyclic nucleotides, adenine and guanine nucleotides, soluble lipid messengers) and mobilization of calcium ions. Consequent to the generation of necessary signals, the insulin-laden secretory granules are transported from distal sites to the plasma membrane for fusion and release of their cargo into the circulation. The secretory granule transport underlies precise changes in cytoskeletal architecture involving a well-coordinated cross-talk between various signaling proteins, including small molecular mass GTP-binding proteins (G proteins) and their respective effector proteins. The purpose of this article is to provide an overview of current understanding of the identity of small G proteins (e.g., Cdc42, Rac1, and ARF-6) and their corresponding regulatory factors (e.g., GDP/GTP-exchange factors, GDP-dissociation inhibitors) in the pancreatic beta-cell. Plausible mechanisms underlying regulation of these signaling proteins by insulin secretagogues are also discussed. In addition to their positive modulatory roles, certain small G proteins also contribute to the metabolic dysfunction and demise of the islet beta-cell seen in in vitro and in vivo models of impaired insulin secretion and diabetes. Emerging evidence also suggests significant insulin secretory abnormalities in small G protein knockout animals, further emphasizing vital roles for these proteins in normal health and function of the islet beta-cell. Potential significance of these experimental observations from multiple laboratories and possible avenues for future research in this area of islet research are highlighted.

中文翻译：

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小 G 蛋白在胰岛 β 细胞功能中的作用。


胰岛β细胞的葡萄糖刺激胰岛素分泌涉及一系列代谢事件以及导致第二信使（例如环核苷酸、腺嘌呤和鸟嘌呤核苷酸、可溶性脂质信使）产生的多种信号传导途径之间的相互作用。钙离子的动员。产生必要的信号后，负载胰岛素的分泌颗粒从远端转运至质膜，进行融合并将其物质释放到循环中。分泌颗粒运输是细胞骨架结构精确变化的基础，涉及各种信号蛋白之间良好协调的串扰，包括小分子质量 GTP 结合蛋白（G 蛋白）及其各自的效应蛋白。本文的目的是概述目前对小 G 蛋白（例如 Cdc42、Rac1 和 ARF-6）及其相应调控因子（例如 GDP/GTP 交换因子、GDP 解离因子）的认识。抑制剂）在胰腺β细胞中。还讨论了胰岛素促分泌剂调节这些信号蛋白的合理机制。除了其积极的调节作用外，某些小 G 蛋白还会导致胰岛 β 细胞的代谢功能障碍和死亡，这在胰岛素分泌受损和糖尿病的体外和体内模型中可见。新出现的证据还表明，小 G 蛋白敲除动物中存在显着的胰岛素分泌异常，进一步强调了这些蛋白在胰岛 β 细胞的正常健康和功能中的重要作用。 强调了来自多个实验室的这些实验观察的潜在意义以及胰岛研究领域未来研究的可能途径。