Glucolipotoxicity-induced Oxidative Stress is Related to Mitochondrial Dysfunction and Apoptosis of Pancreatic β-cell

Glucolipotoxicity-induced oxidative stress and mitochondrial dysfunction of pancreatic beta-cells are some of the mechanisms that have been related to the low insulin secretion and cell death during diabetes development. In early or non-chronic stages, the pancreatic beta-cells respond to hyperglycemia or hyperlipidemia, stimulating insulin secretion. However, the chronic effect of both leads to glucolipotoxicity, which induces constant overstimulation of pancreatic beta-cells, a condition that leads to cell death by apoptosis. The mechanism described, at this moment, is the accelerated mitochondrial dysfunction triggered by the high production of reactive oxygen species (ROS) due to excess nutrients. At first, mitochondria respond to over-nutrition accelerating oxygen consumption and consequently increasing the ATP synthesis. A permanent increase of ATP/ADP ratio leads to a constant inhibition of K+ATP-channel and, therefore, a continuous insulin secretion accompanied by an increase in ROS. Finally, ROS accumulation compromises mitochondrial function due to the uncontrolled oxidation of proteins, lipids, and DNA generating functional alterations such as a drop of membrane potential, deregulation of mitochondrial dynamics, low rate of ATP synthesis and consequently the cell death. This review aims to describe the effect of glucolipotoxicity- induced oxidative stress and its relationship with mitochondrial dysfunction in beta-cell during type 2 diabetes development.

Automated summary

The mechanisms of low insulin secretion and mitochondrial dysfunction in pancreatic beta-cells are related to the development of diabetes. Chronic exposure to high levels of glucose and lipids leads to glucolipotoxicity, which causes overstimulation of beta-cells and ultimately cell death. This review explores the impact of oxidative stress and mitochondrial dysfunction on beta-cells in type 2 diabetes development.