Department of Biotechnology, Faculty of Biotechnology, University of Surabaya, Surabaya, East Java, Indonesia.
Chem Biol Drug Des. 2022 Feb;99(2):344-361. doi: 10.1111/cbdd.13989. Epub 2021 Dec 18.
Diabetes mellitus type 2 (T2D) is one of the metabolic disorders suffered by a global human being. Certain factors, such as lifestyle and heredity, can increase a person's tendency for T2D. Various genes and proteins play a role in the development of insulin resistance and ultimately diabetes in which one central protein that is discussed in this review is FoxO1. In this review, we regard FoxO1 activation as detrimental, promote high plasma glucose level, and induce insulin resistance. Indeed, many contrasting studies arise since FoxO1 is an important protein to alleviate oxidative stress and promote cell survival, for example, also by preventing hyperglycemic-induced cell death. Inter-relation to PPARG, another important protein in metabolism, is also discussed. Ultimately, we discussed contrasting approaches of targeting FoxO1 to combat diabetes mellitus by small molecules.
2 型糖尿病（T2D）是全球人类面临的代谢紊乱之一。某些因素，如生活方式和遗传，会增加人们患 T2D 的倾向。各种基因和蛋白质在胰岛素抵抗和最终糖尿病的发展中发挥作用，其中一个在本综述中讨论的核心蛋白是 FoxO1。在本综述中，我们将 FoxO1 的激活视为有害的，会促进高血糖水平，并诱导胰岛素抵抗。事实上，由于 FoxO1 是一种重要的蛋白质，可以减轻氧化应激并促进细胞存活，例如，还可以防止高血糖引起的细胞死亡，因此出现了许多相互矛盾的研究。还讨论了与另一种代谢重要蛋白 PPARG 的相互关系。最终，我们讨论了通过小分子靶向 FoxO1 来对抗糖尿病的相互矛盾的方法。
