Metformin effects on the heart and the cardiovascular system: A review of experimental and clinical data  L. Nesti, A. Natali  Nutrition, Metabolism and.

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Metformin effects on the heart and the cardiovascular system: A review of experimental and clinical data  L. Nesti, A. Natali  Nutrition, Metabolism and Cardiovascular Diseases  Volume 27, Issue 8, Pages 657-669 (August 2017) DOI: 10.1016/j.numecd.2017.04.009 Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University Terms and Conditions

Figure 1 Effects of metformin on cell metabolism. Intracellular signaling molecules activated by metformin are shown with red continuous lines; those being inhibited are shown with blue dotted lines. The black lines describe the consequences on other substrates or on metabolic pathways (in italics). Blue and red boxes indicate inhibited and activated proteins, respectively. ACC1/2: Acetyl-CoA Carboxylase-1/2. AMPK: AMP-activated protein kinase. FFA: free fatty acids. AKT: also known as protein kinase B. FOxO1: Forkhead box protein 1. GLUT4: glucose transporter 4. PCK-e: protein kinase C-epsilon. PFKFB3: 6-phosphofrutto-2-kinase/fructose-2, 6-biphosphatase 3 kinase. Nutrition, Metabolism and Cardiovascular Diseases 2017 27, 657-669DOI: (10.1016/j.numecd.2017.04.009) Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University Terms and Conditions

Figure 2 Effects of metformin on the vasculature. Metformin can indirectly exert a protective effect on the vasculature mainly by reducing inflammation and oxidative stress and protecting from fibrosis and remodeling. Blue and red indicate inhibition and activation, respectively. AT1R: Angiotensin II receptor 1. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) Nutrition, Metabolism and Cardiovascular Diseases 2017 27, 657-669DOI: (10.1016/j.numecd.2017.04.009) Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University Terms and Conditions

Figure 3 Effects of metformin on the heart. Metformin has been suggested to exert effects on electric activity, cardiomyocyte metabolism, ischemia, remodeling, as well as on myocardial systolic and diastolic functions. For each function, we have summarized the evidence according to the type of experiments. IGT: impaired glucose tolerance. DM: diabetes mellitus. LV: left ventricle. Nutrition, Metabolism and Cardiovascular Diseases 2017 27, 657-669DOI: (10.1016/j.numecd.2017.04.009) Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University Terms and Conditions