Potential roles of PP2A-Rac1 signaling axis in pancreatic β-cell dysfunction under metabolic stress: Progress and promise.
Potential roles of PP2A-Rac1 signaling axis in pancreatic β-cell dysfunction under metabolic stress: Progress and promise.
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DOI：
10.1016/j.bcp.2020.114138
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发表时间：
2020-10
影响因子：
5.8
通讯作者：
Kowluru, Anjaneyulu
中科院分区：
文献类型：
--
作者：
Kowluru, Anjaneyulu
国际糖尿病联合会最近的估计表明，2019年糖尿病的发病率飙升至4.63亿的历史最高水平，该联合会预测，到2045年，患有这种疾病的人数将增加到7亿。因此，努力了解糖尿病的病理生理学是朝着这种疾病的新的治疗策略的发展至关重要。已经提出了导致糖尿病发病的代谢功能障碍和胰岛β细胞死亡的几个因素（氧化应激、内质网应激等）。现有的实验证据显示，暴露于代谢应激（致糖尿病）条件下的胰腺β细胞中PP 2A和Rac 1持续活化。在多种细胞类型中的证据暗示了特定信号蛋白（α4、SET、nm 23-H1、Pak 1）在PP 2A和Rac 1的功能调节中的调节作用。在这篇评论中，我概述了PP 2A和Rac 1信号传导模块在胰岛β细胞代谢失调发作中的潜在串扰，导致葡萄糖刺激的胰岛素分泌受损（GSIS），β细胞质量损失和糖尿病发作。潜在的知识差距和未来的方向，在这个肥沃的领域胰岛生物学也突出显示。希望本综述能为进一步研究PP 2A-Rac 1信号转导模块在胰岛β细胞功能障碍中的作用及寻找治疗糖尿病胰岛β细胞功能障碍的靶点提供基础。PP 2A和Rac 1信号传导模块之间的潜在串扰导致代谢应激条件下胰岛β细胞功能障碍。
Recent estimates by the International Diabetes Federation suggest that the incidence of diabetes soared to an all-time high of 463 million in 2019, and the federation predicts that by 2045 the number of individuals afflicted with this disease will increase to 700 million. Therefore, efforts to understand the pathophysiology of diabetes are critical for moving toward the development of novel therapeutic strategies for this disease. Several contributors (oxidative stress, endoplasmic reticulum stress and others) have been proposed for the onset of metabolic dysfunction and demise of the islet β-cell leading to the pathogenesis of diabetes. Existing experimental evidence revealed sustained activation of PP2A and Rac1 in pancreatic β-cells exposed to metabolic stress (diabetogenic) conditions. Evidence in a variety of cell types implicates modulatory roles for specific signaling proteins (α4, SET, nm23-H1, Pak1) in the functional regulation of PP2A and Rac1. In this Commentary, I overviewed potential cross-talk between PP2A and Rac1 signaling modules in the onset of metabolic dysregulation of the islet β-cell leading to impaired glucose-stimulated insulin secretion (GSIS), loss of β-cell mass and the onset of diabetes. Potential knowledge gaps and future directions in this fertile area of islet biology are also highlighted. It is hoped that this Commentary will provide a basis for future studies toward a better understanding of roles of PP2A-Rac1 signaling module in pancreatic β-cell dysfunction, and identification of therapeutic targets for the treatment of islet β-cell dysfunction in diabetes. Potential cross talk between PP2A and Rac1 signaling modules leading to dysfunction of the islet β-cell under metabolic stress conditions.
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影响因子：
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影响因子：
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