• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemical Pharmacology >Tiaml/Vav2-Racl axis: A tug-of-war between islet function and dysfunction
【24h】

Tiaml/Vav2-Racl axis: A tug-of-war between islet function and dysfunction

机译：TIAML / VAV2-RACL轴：胰岛功能和功能障碍之间的拔河

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Glucose-stimulated insulin secretion [GSIS] from the islet 3-cell involves a well-orchestrated interplay between metabolic and cationic events. It is well established that intracellular generation of adenine and guanine nucleotide triphosphates [e.g., ATP and GTP] represents one of the requisite signaling steps in GSIS. The small molecular mass GTP-binding proteins [G-proteins; e.g., Racl and Cdc42] have been shown to regulate islet 8-cell function including actin cytoskeletal remodeling and fusion of insulin granules with the plasma membrane for GSIS to occur. In this context, several regulatory factors for these G-proteins have been identified in the pancreatic 8-cell; these include guanine nucleotide exchange factors [GEFs] and guanine nucleotide dissociation inhibitors [GDI]. Recent pharmacological and molecular biological evidence identified Tiam1 and Vav2 as GEFs for Racl in promoting physiological insulin secretion. Paradoxically, emerging evidence in multiple cell types, including the islet 3-cell, suggests key roles for Racl in the onset of cellular dysfunction under conditions of metabolic stress and diabetes. Furthermore, functional inactivation of either Tiam1 or Vav2 appears to attenuate sustained activation of Rac1 and its downstream signaling events [activation of stress kinases] under conditions of metabolic stress. Together, these findings suggest both "friendly" and "non-friendly" roles for Tiaml/Vav2-Racl signaling axis in islet 8-cell in health and diabetes. Our current understanding of the field and the knowledge gaps that exist in this area of islet biology are heighted herein. Furthermore, potential caveats in the specificity and selectivity of pharmacological inhibitors that are available currently are discussed in this Commentary. Published by Elsevier Inc.
机译：来自胰岛3细胞的葡萄糖刺激的胰岛素分泌[GSIS]涉及代谢和阳离子事件之间的策划良好的相互作用。很好地确定，细胞内产生腺嘌呤和鸟嘌呤核苷酸三磷酸酯[例如，ATP和GTP]代表GSI中的必要信号步骤之一。小分子量GTP结合蛋白[G-蛋白;例如，已经证明了Rac1和CDC42，用于调节胰岛8细胞功能，包括肌动蛋白细胞骨架重塑和胰岛素颗粒的融合与用于GSI的质子膜。在这种情况下，已在胰腺8细胞中鉴定出这些G-蛋白的几个调节因子;这些包括鸟嘌呤核苷酸交换因子[GEFS]和鸟嘌呤核苷酸解离抑制剂[GDI]。最近的药理学和分子生物学证据确定了TIAM1和VAV2作为促进生理胰岛素分泌的RACL的GEF。矛盾的是，包括胰岛3细胞的多种细胞类型的新出现证据表明在代谢应激和糖尿病条件下的细胞功能障碍发作中的RACL的关键作用。此外，TIAM1或VAV2的功能灭活似乎在代谢应力的条件下衰减了RAC1及其下游信号传导事件的持续激活[应激激酶的激活]。这些研究结果在一起，建议在健康和糖尿病中的胰岛8细胞中的TIAML / VAV2-RACL信号轴“友好”和“不友好”角色。我们目前对该领域的理解及其在胰岛生物学领域存在的知识间隙在此处高。此外，目前可获得的药理抑制剂的特异性和选择性的潜在警告在该评论中讨论。 elsevier公司发布

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号