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

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