Department of Advanced Medical and Surgical Sciences - University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Department of Advanced Medical and Surgical Sciences - University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Pharmacol Res. 2022 Feb;176:106062. doi: 10.1016/j.phrs.2022.106062. Epub 2022 Jan 10.
Gliflozins are a novel class of oral anti-diabetic drugs, acting as inhibitors of sodium-glucose co-transporters (SGLTs) through the proximal convoluted tubules (PCT) and intestinal epithelium. The sodium-glucose co-transporters 2 (SGLT2) are mainly expressed in S1 and S2 segments of the proximal convoluted tubule in the kidneys. Clinical guidelines recommend their use especially in Type 2 Diabetes mellitus (T2DM) patients with vascular complications and/or heart failure highlighting the importance of sodium-glucose co-transporter 2 inhibitors (SGLT2i) pleiotropic effects. Interestingly, cognitive decline is a widely recognized complication of T2DM and, in addition, to clarify its pathophysiology, there is an urgent need to understand how and if diabetes therapies can control diabetes-related cognitive dysfunction. At the time, although SGLT2 proteins are present in the Central Nervous System (CNS), the SGLT2i effects on cognitive impairments remain partly unknown. In pre-clinical studies, SGLT2i ameliorates cognitive dysfunction in obese and T2DM mice, reducing oxidative stress, neuroinflammation and improving neuronal plasticity and mitochondrial brain pathway. In addition, SGLT2i could bring back mTOR to a physiological state of activation, stopping neurodegenerative diseases' onset or progression. Instead, clinical studies on T2DM-related cognitive dysfunction treated by SGLT2i are much more limited. For these reasons, further studies are needed to better elucidate if SGLT2i therapy can affect T2DM-related cognitive decline. In this scenario, this review aims to summarize the state of knowledge on the role of SGLT2i in T2DM-related cognitive dysfunction and stimulate new clinical trials.
格列净类是一类新型的口服降糖药物，通过近曲小管（PCT）和肠上皮作为钠-葡萄糖协同转运蛋白（SGLT）的抑制剂。钠-葡萄糖协同转运蛋白 2（SGLT2）主要表达于肾脏近曲小管 S1 和 S2 段。临床指南建议将其特别用于有血管并发症和/或心力衰竭的 2 型糖尿病（T2DM）患者，突出了钠-葡萄糖协同转运蛋白 2 抑制剂（SGLT2i）的多效性作用的重要性。有趣的是，认知能力下降是 T2DM 的广泛公认的并发症，此外，为了阐明其病理生理学，迫切需要了解糖尿病疗法如何以及是否可以控制与糖尿病相关的认知功能障碍。尽管 SGLT2 蛋白存在于中枢神经系统（CNS）中，但 SGLT2i 对认知障碍的影响仍部分未知。在临床前研究中，SGLT2i 改善肥胖和 T2DM 小鼠的认知功能障碍，减少氧化应激、神经炎症，并改善神经元可塑性和线粒体脑途径。此外，SGLT2i 可以使 mTOR 恢复到生理激活状态，阻止神经退行性疾病的发生或进展。相反，用 SGLT2i 治疗 T2DM 相关认知功能障碍的临床研究要少得多。出于这些原因，需要进一步的研究来更好地阐明 SGLT2i 治疗是否可以影响 T2DM 相关的认知衰退。在这种情况下，本综述旨在总结 SGLT2i 在 T2DM 相关认知功能障碍中的作用的现有知识，并激发新的临床试验。
