Oxidative stress in diabetes: implications for vascular and other complications

Abstract

In recent decades, oxidative stress has become a focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence shows that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on these studies, an emerging concept is that oxidative stress is the "final common pathway" through which the risk factors for several diseases exert their deleterious effects. Oxidative stress causes a complex dysregulation of cell metabolism and cell-cell homeostasis; in particular, oxidative stress plays a key role in the pathogenesis of insulin resistance and β-cell dysfunction. These are the two most relevant mechanisms in the pathophysiology of type 2 diabetes and its vascular complications, the leading cause of death in diabetic patients.

Figure 1

Proposed mechanisms by which increased oxidative stress in diabetes may lead to insulin resistance and atherosclerosis. All abbreviations are spelled out in the text. ↑ indicates increased levels; ↓ indicates decreased levels.

Figure 2

Vascular effects of insulin in the healthy state and in conditions characterized by increased oxidative stress and insulin resistance. PVAT indicates perivascular adipose tissue, all other abbreviations are spelled out in the text.

Figure 3

Schematic representation of the pathophysiological role of AGE accumulation and increased oxidative stress in diabetic complications like retinopathy, nephropaty and neuropathy. All abbreviations are spelled out in the text. ↑ indicates increased levels; ↓ indicates decreased levels.