Glucolipotoxicity-induced oxidative stress is related to mitochondrial dysfunction and apoptosis of pancreatic ß-cell Academic Article in Scopus uri icon

abstract

  • © 2021 Bentham Science Publishers.Glucolipotoxicity-induced oxidative stress and mitochondrial dysfunction of pancreatic ß-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 ß-cells respond to hyperglycemia or hyperlipidemia, stimulating insulin secretion. However, the chronic effect of both leads to glucolipotoxicity, which induces constant overstimulation of pancreatic ß-cells, a condition that leads to cell death by apoptosis. The mechanism described, at this moment, is the accel-erated 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 ac-companied 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 glucolipo-toxicity-induced oxidative stress and its relationship with mitochondrial dysfunction in ß-cell during type 2 diabetes development.

publication date

  • January 1, 2021