Type 2 Diabetes and Breast Cancer: The Interplay between Impaired Glucose Metabolism and Oxidant Stress

Figure 1

Pathways of oxidative stress associated with diabetes mellitus: mechanisms of carcinogenesis. Type 2 diabetes (T2D) causes both hyperglycaemia and hyperinsulinemia/IR. Hyperglycemia may induce reactive oxygen species (ROS) production directly via glucose metabolism and autooxidation and indirectly through the formation of advanced glycation end products (AGE) and their receptor (RAGE) binding. ROS, in turn, may exert their effects on DNA, through activation of signaling molecules (i.e., nuclear transcription factor-B—NF-B) and subsequent transcription of genes encoding cytokines and adhesive proteins. Hyperinsulinemia, insulin resistance (IR) and insulin-like growth factor-1 (IGF-1) activate signaling pathways, such as mitogen-activated protein kinase (MAPK) and AKT signaling pathways, that lead to carcinogenesis.