Figure 1. Mitochondrial stress in type 2 diabetes and obesity. The current lifestyle of overconsumption and physical inactivity poses a persistent nutrient surplus, leading to mitochondrial stress and the accumulation of reactive oxygen species (ROS) and metabolite intermediates (FFA and DAG) that can trigger oxidative stress and activation of stress-sensitive kinases. Impaired insulin secretion and sensitivity (i.e., the hallmarks of T2DM) occur as a result of stress-induced β-cell dysfunction and insulin resistance. FFA, free fatty acid; DAG, diacylglycerol.