Affiliation:
1. Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, N.L., Mexico
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.
Publisher
Bentham Science Publishers Ltd.
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism
Cited by
22 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献