Birla Institute of Technology & Science- Pilani, Hyderabad Campus, Department of Pharmacy, Drug Discovery Research Laboratory, R.R. District-500078, Andhra Pradesh, India.
Expert Opin Ther Targets. 2012 Aug;16(8):819-32. doi: 10.1517/14728222.2012.703656. Epub 2012 Jul 5.
Dysregulation of metabolic pathways, caused by imbalances in energy homeostasis, leads to type 2 diabetes characterized by high glucose concentration in the blood due to insulin resistance which is a major disorder in developed countries.
One of the recent treatment strategies is using activators of SIRT1, which has been in clinical trials. Many of the cellular processes including insulin secretion, cell cycle, and apoptosis are imperatively regulated by a family of mediators called sirtuins. First known mammalian sirtuin, SIRT1 is a positive regulator of insulin secretion, which triggers glucose uptake and utilization. Since the past decade, a major outstanding question is whether SIRT1 activation is a safe therapy for human diseases such as type 2 diabetes? This review summarizes and discusses the advances of the past decade and the challenges that will brazen out perplexity about homeostasis and metabolic pathways linked to SIRT1 and type 2 diabetes. Furthermore, we described the interlink between SIRT1 metabolic pathways of various tissues such as pancreas, skeletal muscle, adipose tissue and liver.
However be the complexity of the pathways involved, T2DM regulated by SIRT1 affected metabolism is dropping down progressively due to profound research. In the context of interlinking all the SIRT1 pathways in T2DM we found various crucial intermediaries in metabolic tissues, which can also be targeted for future prospects.
由于能量平衡失调导致代谢途径紊乱,会引发 2 型糖尿病,其特征是由于胰岛素抵抗导致血液中葡萄糖浓度升高,而胰岛素抵抗是发达国家的主要疾病。
最近的治疗策略之一是使用 SIRT1 激活剂,该策略已在临床试验中进行。许多细胞过程,包括胰岛素分泌、细胞周期和细胞凋亡,都受到一类称为沉默调节蛋白的介质的严格调节。SIRT1 是第一个被发现的哺乳动物沉默调节蛋白,它是胰岛素分泌的正调节剂,可触发葡萄糖摄取和利用。在过去的十年中,一个主要的悬而未决的问题是 SIRT1 激活是否是治疗 2 型糖尿病等人类疾病的安全疗法?本文综述和讨论了过去十年的进展,以及与 SIRT1 和 2 型糖尿病相关的稳态和代谢途径的挑战。此外,我们描述了各种组织(如胰腺、骨骼肌、脂肪组织和肝脏)中 SIRT1 代谢途径之间的相互联系。
尽管涉及的途径很复杂,但由于深入的研究,受 SIRT1 调节的 2 型糖尿病的代谢正在逐步下降。在联系 2 型糖尿病中所有 SIRT1 途径的背景下,我们在代谢组织中发现了各种关键的中间产物,这些中间产物也可以作为未来的研究目标。