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SGLT1 抑制剂对糖尿病相关心肌病的影响是好是坏。

SGLT1 inhibition boon or bane for diabetes-associated cardiomyopathy.

机构信息

Department of Pharmacy, Birla Institute of Technology and Sciences (BITS) Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad,, Andhra Pradesh, 500078, India.

Centre for Molecular Biology, Central University of Jammu, Jammu, 181143, India.

出版信息

Fundam Clin Pharmacol. 2020 Apr;34(2):173-188. doi: 10.1111/fcp.12516. Epub 2019 Nov 19.

Abstract

Chronic hyperglycaemia is a peculiar feature of diabetes mellitus (DM). Sequential metabolic abnormalities accompanying glucotoxicity are some of its implications. Glucotoxicity most likely corresponds to the vascular intricacy and metabolic alterations, such as increased oxidation of free fatty acids and reduced glucose oxidation. More than half of those with diabetes also develop cardiac abnormalities due to unknown causes, posing a major threat to the currently available marketed preparations which are being used for treating these cardiac complications. Even though impairment in cardiac functioning is the principal cause of death in individuals with type 2 diabetes (T2D), reducing plasma glucose levels has little effect on cardiovascular disease (CVD) risk. In vitro and in vivo studies have demonstrated that inhibitors of sodium glucose transporter (SGLT) represent a putative therapeutic intervention for these pathological conditions. Several clinical trials have reported the efficacy of SGLT inhibitors as a novel and potent antidiabetic agent which along with its antihyperglycaemic activity possesses the potential of effectively treating its associated cardiac abnormalities. Thus, hereby, the present review highlights the role of SGLT inhibitors as a successful drug candidate for correcting the shifts in deregulation of cardiac energy substrate metabolism together with its role in treating diabetes-related cardiac perturbations.

摘要

慢性高血糖是糖尿病(DM)的一个特殊特征。伴随糖毒性的连续代谢异常是其影响之一。糖毒性最可能对应于血管复杂性和代谢改变,例如增加游离脂肪酸的氧化和减少葡萄糖氧化。由于未知原因,超过一半的糖尿病患者还会出现心脏异常,这对目前用于治疗这些心脏并发症的市售制剂构成了重大威胁。尽管心脏功能障碍是 2 型糖尿病(T2D)患者死亡的主要原因,但降低血浆葡萄糖水平对心血管疾病(CVD)风险几乎没有影响。体外和体内研究表明,钠-葡萄糖共转运蛋白(SGLT)抑制剂是这些病理状况的潜在治疗干预措施。几项临床试验报告了 SGLT 抑制剂的疗效,作为一种新型有效的抗糖尿病药物,除了具有降血糖作用外,还具有有效治疗相关心脏异常的潜力。因此,本综述强调了 SGLT 抑制剂作为一种成功的候选药物,可纠正心脏能量底物代谢失调,并在治疗与糖尿病相关的心脏紊乱方面发挥作用。

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