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糖尿病的脑血管并发症:SGLT-2 抑制剂作为一种有前途的未来治疗方法。

Cerebrovascular Complications of Diabetes: SGLT-2 Inhibitors as a Promising Future Therapeutics.

机构信息

Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmadabad, Gujarat, India.

出版信息

Curr Drug Targets. 2021;22(14):1629-1636. doi: 10.2174/1389450121666201020163454.

DOI:10.2174/1389450121666201020163454
PMID:33081674
Abstract

Sodium-Glucose co-transporter inhibitors are a novel class of drugs widely used in the treatment of type 2 diabetes mellitus medical management. This class of drugs has a simple mechanism of action by which they decrease blood glucose levels. They prevent the uptake or re-absorption of glucose in the blood by inhibiting the SGLT2 co-transport channels located in the renal proximal convoluted tubule. Since SGLT2 is the low affinity, high capacity glucose transporter, it allows the co-transport of sodium and glucose through it. SGLT2s are accountable for around 90% of the renal glucose reuptake. Cerebrovascular complications or accidents (CVAs) are the world's leading cause of mortality, resulting in around 6 million deaths annually. Diabetics are prone to develop mitochondrial dysfunction and neurodegeneration due to hyperglycemia and oxidative stress end products. Due to hyperglycemic condition in diabetes, it is always an elevated risk of cerebrovascular dysfunction due to hyperglycemia as it includes endothelial dysfunction, atherosclerosis, hypercoagulability, oxidative stress, renal reperfusion injury which may lead to neuronal degeneration and cognitive impairment. A diabetic individual is more prone to develop risk factors for transient ischemic attacks than a non-diabetic patient. These inhibitors reduce hyperglycemia by blocking renal glucose reabsorption, therefore promoting an increase in renal glucose excretion. This review discusses the potential role of SGLT2 inhibitors in treating CVAs associated with T2DM.

摘要

钠-葡萄糖共转运蛋白抑制剂是一类广泛用于 2 型糖尿病治疗的新型药物。这类药物的作用机制很简单,即降低血糖水平。它们通过抑制位于肾脏近曲小管的 SGLT2 共转运体通道,阻止葡萄糖在血液中的摄取或重吸收。由于 SGLT2 是低亲和力、高容量的葡萄糖转运蛋白,它允许钠和葡萄糖通过它共转运。SGLT2s 负责约 90%的肾脏葡萄糖重吸收。脑血管并发症或事故 (CVAs) 是全球主要的死亡原因,每年导致约 600 万人死亡。由于高血糖和氧化应激产物,糖尿病患者易发生线粒体功能障碍和神经退行性变。由于糖尿病患者血糖升高,由于内皮功能障碍、动脉粥样硬化、高凝状态、氧化应激、肾再灌注损伤等原因,始终存在脑血管功能障碍的高风险,这可能导致神经元变性和认知障碍。与非糖尿病患者相比,糖尿病个体更容易发生短暂性脑缺血发作的危险因素。这些抑制剂通过阻断肾脏葡萄糖重吸收来降低高血糖,从而促进肾脏葡萄糖排泄增加。本文综述了 SGLT2 抑制剂在治疗与 T2DM 相关的 CVA 中的潜在作用。

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