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

[ Vol. 17 , Issue. 5 ]

Author(s):

Jorge E. Vela-Guajardo, Salvador Garza-González and Noemí García*   Pages 7 - 17 ( 11 )

Abstract:


Glucolipotoxicity-induced oxidative stress and mitochondrial dysfunction of pancreatic β-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 β-cells respond to hyperglycemia or hyperlipidemia, stimulating insulin secretion. However, the chronic effect of both leads to glucolipotoxicity, which induces constant overstimulation of pancreatic β-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 β-cell during type 2 diabetes development.

Keywords:

Insulin, mitochondrial dynamics, type 2 diabetes, metabolism, obesity, hyperglycemia, and hyperlipidemia.

Affiliation:

Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, N.L., Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, N.L., Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, N.L.



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