Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, 610041 Chengdu, China.
Department of Physiology and Biophysics, Mississippi Center for Heart Research, University of Mississippi Medical Center, 39216 Jackson, MS, U.S.A.
Biosci Rep. 2019 Feb 15;39(2). doi: 10.1042/BSR20181995. Print 2019 Feb 28.
Diabetics have higher morbidity and mortality in cardiovascular disease (CVD). A variety of antidiabetic agents are available for clinical choice. Cardiovascular (CV) safety assessment of these agents is crucial in addition to hypoglycemic effect before clinical prescription. Adenosine 5'-monophosphate-activated protein kinase (AMPK) is an important cell energy sensor, which plays an important role in regulating myocardial energy metabolism, reducing ischemia and ischemia/reperfusion (I/R) injury, improving heart failure (HF) and ventricular remodeling, ameliorating vascular endothelial dysfunction, antichronic inflammation, anti-apoptosis, and regulating autophagy. In this review, we summarized the effects of antidiabetic agents to CVD according to basic and clinical research evidence and put emphasis on whether these agents can play roles in CV system through AMPK-dependent signaling pathways. Metformin has displayed definite CV benefits related to AMPK. Sodium-glucose cotransporter 2 inhibitors also demonstrate sufficient clinical evidence for CV protection, but the mechanisms need further exploration. Glucagon-likepeptide1 analogs, dipeptidyl peptidase-4 inhibitors, α-glucosidase inhibitors and thiazolidinediones also show some AMPK-dependent CV benefits. Sulfonylureas and meglitinides may be unfavorable to CV system. AMPK is becoming a promising target for the treatment of diabetes, metabolic syndrome and CVD. But there are still some questions to be answered.
糖尿病患者在心血管疾病（CVD）中的发病率和死亡率更高。有多种抗糖尿病药物可供临床选择。除了低血糖作用外，这些药物的心血管（CV）安全性评估在临床处方前至关重要。腺苷 5'-单磷酸激活蛋白激酶（AMPK）是一种重要的细胞能量传感器，在调节心肌能量代谢、减少缺血和缺血/再灌注（I/R）损伤、改善心力衰竭（HF）和心室重构、改善血管内皮功能障碍、抗炎、抗凋亡以及调节自噬方面发挥着重要作用。在这篇综述中，我们根据基础和临床研究证据总结了抗糖尿病药物对 CVD 的影响，并强调了这些药物是否可以通过 AMPK 依赖性信号通路在 CV 系统中发挥作用。二甲双胍具有明确的与 AMPK 相关的 CV 益处。钠-葡萄糖共转运蛋白 2 抑制剂也为 CV 保护提供了充分的临床证据，但机制仍需进一步探索。胰高血糖素样肽 1 类似物、二肽基肽酶-4 抑制剂、α-葡萄糖苷酶抑制剂和噻唑烷二酮类药物也显示出一些 AMPK 依赖性 CV 益处。磺酰脲类和米格列醇类可能对 CV 系统不利。AMPK 正成为治疗糖尿病、代谢综合征和 CVD 的有前途的靶点。但仍有一些问题需要回答。
