Department of Bioscience and Biotechnology, Banasthali University, Vanasthali, Rajasthan- 304022, India.
University College of Technology, Osmania University, Hyderabad-5000 07, Telangana, India.
Curr Drug Targets. 2021;22(13):1555-1567. doi: 10.2174/1389450122666210120144428.
In India as well as globally, diabetes is in a state of high risk and next to cardiovascular disease. As per the WHO, the risk of diabetes is expected to rise about 511 million by 2030. In quest of novel targets for type-2 diabetes, many targets were elucidated, such as Glycogen Synthase Kinase-3 (GSK-3), Dipeptidyl Peptidase (DPP-IV), PPAR-γ, α-Glucosidase, α-Amylase, GLP-1, and SGLT. Among the targets, GSK-3 was reported to be an effective target for the treatment of diabetes. In the metabolism of glycogen, GSK is a regulatory enzyme for the biosynthesis of glycogen (glycogenesis). It catalyzes the synthesis of a linear unbranched molecule with 1,4-α-glycosidic linkages. GSK-3 family has two isoenzymes, namely α and β, which differ in their Nand C- terminal sequences and are semi-conservative multifunctional serine/threonine kinase enzymes. In this chapter, we discuss an overview of general diabetic mechanisms and how GSK-3 modulation may influence these processes. Mutation in the GSK-3 complex causes diabetes. Synthetic and natural scaffolds modulate GSK-3 against diabetes and leading to its optimization for the development of GSK-3 inhibitors. This review mainly focuses on the development of GSK-3 inhibitors and highlights current and potential future therapeutic approaches that support the notion of targeting glucose metabolism with novel antidiabetic agents.
在印度乃至全球，糖尿病都处于高危状态，仅次于心血管疾病。根据世界卫生组织的数据，到 2030 年，糖尿病的风险预计将上升约 5.11 亿。为了寻找 2 型糖尿病的新靶点，已经阐明了许多靶点，如糖原合酶激酶-3（GSK-3）、二肽基肽酶（DPP-IV）、过氧化物酶体增殖物激活受体-γ（PPAR-γ）、α-葡萄糖苷酶、α-淀粉酶、GLP-1 和 SGLT。在这些靶点中，GSK-3 被报道为治疗糖尿病的有效靶点。在糖原代谢中，GSK 是糖原生物合成（糖生成）的调节酶。它催化具有 1,4-α-糖苷键的线性无分支分子的合成。GSK-3 家族有两种同工酶，即α和β，它们在 N 和 C 末端序列上有所不同，是半保守多功能丝氨酸/苏氨酸激酶酶。在本章中，我们讨论了一般糖尿病机制的概述，以及 GSK-3 调节如何影响这些过程。GSK-3 复合物的突变会导致糖尿病。合成和天然支架调节 GSK-3 以对抗糖尿病，并使其针对 GSK-3 抑制剂的开发进行优化。本综述主要集中于 GSK-3 抑制剂的开发，并强调了当前和潜在的未来治疗方法，这些方法支持了用新型抗糖尿病药物靶向葡萄糖代谢的观点。
