Abstract
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.
Highlights
The prevalence of diabetes has been growing rapidly over the past 20 years
In 2012, about 1.5 million people died of diabetes in the world, of which about 80% were associated with myocardial infarction (MI) or stroke [4]
Our studies have suggested that activated protein C could activate adenosine -monophosphate-activated protein kinase (AMPK) and protect the heart from ischemia/reperfusion (I/R) injury [20], and inhibit inflammatory responses during hypoxia/reoxygenation (H/R) by modulating a JNK-mediated nuclear factor κB (NF-κB) pathway [21]
Summary
AMPK is associated with the beneficial effects of antidiabetic agents on cardiovascular diseases. 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. 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. Glucagon-likepeptide analogs, dipeptidyl peptidase-4 inhibitors, α-glucosidase inhibitors and thiazolidinediones show some AMPK-dependent CV benefits. AMPK is becoming a promising target for the treatment of diabetes, metabolic syndrome and CVD. Accepted Manuscript Online: 01 February 2019 Version of Record published: 15 February 2019
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