Endothelial Dysfunction in Diabetes

Abstract

Diabetes is a worldwide health issue closely associated with cardiovascular events. Given the pandemic of obesity, the identification of the basic underpinnings of vascular disease is strongly needed. Emerging evidence has suggested that endothelial dysfunction is a critical step in the progression of atherosclerosis. However, how diabetes affects the endothelium is poorly understood. Experimental and clinical studies have illuminated the tight link between insulin resistance and endothelial dysfunction. In addition, macrophage polarization from M2 towards M1 contributes to the process of endothelial damage. The possibility that novel classes of anti-hyperglycemic agents exert beneficial effects on the endothelial function and macrophage polarization has been raised. In this review, we discuss the current status of knowledge regarding the pathological significance of insulin signaling in endothelium. Finally, we summarize recent therapeutic strategies against endothelial dysfunction with an emphasis on macrophage polarity.

Keywords: endothelial dysfunction; insulin resistance; macrophage polarity.

Figure 1

The metabolic network between macrophage polarization, insulin resistance, and endothelial cells. Macrophages play pleiotropic functions in the endothelium. Proinflammatory M1 macrophages are stimulated by LPS, IFN-γ, and TNF-α and promote the secretion of inflammatory cytokines, including IL-1, IL-6, and TNF-α. In contrast, anti-inflammatory M2 macrophages are stimulated by IL-4 and IL-10 and secrete anti-inflammatory cytokines, such as IL-10 and TGF-β. Through NO/VASP signaling, M2 macrophages contribute to the suppression of inflammation in the endothelium, leading to the improvement of insulin resistance and endothelial dysfunction. NO, Nitric oxide; VASP, Vasodilator-stimulated phosphoprotein.