Does the glucose-dependent insulin secretion mechanism itself cause oxidative stress in pancreatic β-cells?
Does the glucose-dependent insulin secretion mechanism itself cause oxidative stress in pancreatic β-cells?
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DOI：
10.2337/diabetes.53.8.1942
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发表时间：
2004-08-01
期刊：
影响因子：
7.7
通讯作者：
Philipson, LH
中科院分区：
文献类型：
--
作者：
Fridlyand, LE;Philipson, LH
胰腺β细胞中的葡萄糖依赖性胰岛素分泌（GDIS）、活性氧（ROS）产生和氧化应激可能是紧密相关的过程。在这里，我们认为，在GDIS的激活（增加糖酵解通量，ATP-ADP比，和细胞内Ca 2+浓度）中使用的相同的途径可以显着提高ROS的生产和氧化应激的表现，并可能，凋亡。GDIS激活本身产生的ROS产生和氧化应激的增加表明代谢性胰岛素促分泌素的双重作用，因为胰岛素分泌速率的初始急剧增加可伴随进行性β细胞损伤。我们建议，针对增强GDIS的治疗策略应仔细考虑β细胞功能和质量的可能损失。
Glucose-dependent insulin secretion (GDIS), reactive oxygen species (ROS) production, and oxidative stress in pancreatic beta-cells may be tightly linked processes. Here we suggest that the same pathways used in the activation of GDIS (increased glycolytic flux, ATP-to-ADP ratio, and intracellular Ca2+ concentration) can dramatically enhance ROS production and manifestations of oxidative stress and, possibly, apoptosis. The increase in ROS production and oxidative stress produced by GDIS activation itself suggests a dual role for metabolic insulin secretagogues, as an initial sharp increase in insulin secretion rate can be accompanied by progressive beta-cell injury. We propose that therapeutic strategies targeting enhancement of GDIS should be carefully considered in light of possible loss of beta-cell function and mass.