School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia.
Department of Pharmacology and Therapeutics, School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia; Department of Pharmacology and Therapeutics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, 3010, Australia; Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), Bukit Gambir, Gelugor, Pulau Pinang, Malaysia.
Eur J Pharmacol. 2021 Jan 15;891:173758. doi: 10.1016/j.ejphar.2020.173758. Epub 2020 Nov 27.
Glucose production and the consumption of high levels of carbohydrate increase the chance of insulin resistance, especially in cases of obesity. Therefore, maintaining a balanced glucose homeostasis might form a strategy to prevent or cure diabetes and obesity. The activation and inhibition of glucose production is complicated due to the presence of many interfering pathways. These pathways can be viewed at the downstream level because they activate certain transcription factors, which include the Forkhead-O1 (FoxO1). This has been identified as a significant agent in the pancreas, liver, and adipose tissue, which is significant in the regulation of lipids and glucose. The objective of this review is to discuss the intersecting portrayal of FoxO1 and its parallel cross-talk which highlights obesity-induced insulin susceptibility in the discovery of a targeted remedy. The review also analyses current progress and provides a blueprint on therapeutics, small molecules, and extracts/phytochemicals which are explored at the pre-clinical level.
葡萄糖的产生和高水平碳水化合物的消耗会增加胰岛素抵抗的几率,尤其是在肥胖的情况下。因此,维持葡萄糖的平衡可能是预防或治疗糖尿病和肥胖的一种策略。由于存在许多干扰途径,葡萄糖的产生的激活和抑制变得复杂。这些途径可以在下游水平上观察到,因为它们会激活某些转录因子,包括叉头框蛋白 O1(FoxO1)。FoxO1 已被确定为胰腺、肝脏和脂肪组织中重要的调节因子,在调节脂质和葡萄糖方面具有重要作用。本综述的目的是讨论 FoxO1 的相互交织的作用及其平行的串扰,突出肥胖诱导的胰岛素敏感性在靶向治疗发现中的作用。该综述还分析了当前的进展,并提供了一个蓝图,阐述了在临床前水平探索的治疗方法、小分子以及提取物/植物化学物质。