The role of alternative splicing and splicing factors in diabetes: Current status and future perspectives

WIREs RNA Pub Date : 2024-01-01 DOI:10.1002/wrna.1831

Didhiti Singha, Meghna Mondal, Dhruba Ghosh, Debopriya Choudhury, Bandana Chakravarti, Rajesh Kumar Kar, Pushkar Malakar

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Abstract

With glucose being at the center of energy consumption and production, maintaining homeostasis of this simple sugar is of pivotal importance. Loss of glucose homeostasis results in altered blood glucose levels, that are frequently observed in type 2 diabetes (T2D) and obesity. T2D and obesity share pathophysiological mechanisms and genetic backgrounds. These conditions collectively impact over 500 million individuals worldwide, necessitating a deeper mechanistic understanding for effective therapeutic strategies. Recent studies have highlighted the involvement of abnormal alternative splicing (AS) and changes in splicing factors (SFs) in the development and progression of diabetic conditions, presenting AS and SFs as promising targets for therapy. This review focuses on the deregulation of AS (INSR, TCF7L2, and mTOR) and SF (Sam68) deregulation in diabetic conditions. In addition, we discuss the importance of mTOR signaling in diabetic conditions and its regulation by AS and SFs. Furthermore, we discuss current strategies aimed at targeting AS and SFs. Finally, we discuss research challenges, and unresolved questions in the field, and offer recommendations to enhance our comprehension of the significance of AS and SFs in the context of diabetes and obesity.This article is categorized under: RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing RNA in Disease and Development > RNA in Disease

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替代剪接和剪接因子在糖尿病中的作用：现状与未来展望

葡萄糖是能量消耗和产生的核心，因此保持这种单糖的平衡至关重要。葡萄糖平衡失调会导致血糖水平改变，这在 2 型糖尿病（T2D）和肥胖症中经常出现。2 型糖尿病和肥胖症具有相同的病理生理机制和遗传背景。这些病症共同影响着全球 5 亿多人，因此有必要加深对其机理的了解，以制定有效的治疗策略。最近的研究强调，异常替代剪接（AS）和剪接因子（SFs）的变化参与了糖尿病病症的发生和发展，并将 AS 和 SFs 作为有希望的治疗靶点。本综述将重点讨论糖尿病病症中 AS（INSR、TCF7L2 和 mTOR）和 SF（Sam68）的失调。此外，我们还讨论了 mTOR 信号在糖尿病病症中的重要性以及 AS 和 SF 对其的调控。此外，我们还讨论了当前针对 AS 和 SF 的策略。最后，我们讨论了该领域的研究挑战和悬而未决的问题，并提出了建议，以提高我们对 AS 和 SFs 在糖尿病和肥胖症中的重要性的理解。本文分类：RNA 处理 > 剪接机制RNA 处理 > 剪接调控/替代剪接RNA 在疾病和发育中的作用 > RNA 在疾病中的作用

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