Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Diabetes

It is generally accepted that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are related to insulin resistance and type 2 diabetes. Mitochondria use substrates from lipid and glucose metabolism in order to generate ATP, and when mitochondrial O2 consumption is decreased due to an altered metabolism there is an increase in reactive oxygen species (ROS) that can impair different types of molecules and cells, especially in β- cells during type 2 diabetes. Furthermore, the maintenance of ER function in insulin-secreting β-cells is crucial, and when ER homeostasis is disrupted, the ER develops an unfolded protein response (UPR) in order to maintain the homeostasis of this organelle. However, when homeostasis fails in mitochondria and ER, these organelles can initiate death signalling pathways. New research has suggested that hyperlipidemia and hyperliglucaemia, known as key factors of type 2 diabetes (T2D), disrupt mitochondrial activity and ER homeostasis, thus triggering a disruption of energy metabolism, unresolvable UPR activation and β-cell death. This review explains the mechanisms of mitochondrial function and ER stress related to the pathological effects of type 2 diabetes in different tissues.