Suppr超能文献

遗传背景对小鼠胰岛氧化应激诱导及胰岛素分泌受损的影响。

The influence of genetic background on the induction of oxidative stress and impaired insulin secretion in mouse islets.

作者信息

Zraika S, Aston-Mourney K, Laybutt D R, Kebede M, Dunlop M E, Proietto J, Andrikopoulos S

机构信息

Department of Medicine (AH/NH), University of Melbourne, Heidelberg Repatriation Hospital, Heidelberg Heights, VIC 3081, Australia.

出版信息

Diabetologia. 2006 Jun;49(6):1254-63. doi: 10.1007/s00125-006-0212-9. Epub 2006 Mar 29.

Abstract

AIMS/HYPOTHESIS: We determined whether high-glucose-induced beta cell dysfunction is associated with oxidative stress in the DBA/2 mouse, a mouse strain susceptible to islet failure.

MATERIALS AND METHODS

Glucose- and non-glucose-mediated insulin secretion from the islets of DBA/2 and control C57BL/6 mice was determined following a 48-h exposure to high glucose. Flux via the hexosamine biosynthesis pathway was assessed by determining O-glycosylated protein levels. Oxidative stress was determined by measuring hydrogen peroxide levels and the expression of anti-oxidant enzymes.

RESULTS

Exposure to high glucose levels impaired glucose-stimulated insulin secretion in DBA/2 islets but not C57BL/6 islets, and this was associated with reduced islet insulin content and lower ATP levels than in C57BL/6 islets. Exposure of islets to glucosamine for 48 h mimicked the effects of high glucose on insulin secretion in the DBA/2 islets. High glucose exposure elevated O-glycosylated proteins; however, this occurred in islets from both strains, excluding a role for O-glycosylation in the impairment of DBA/2 insulin secretion. Additionally, both glucosamine and high glucose caused an increase in hydrogen peroxide in DBA/2 islets but not in C57BL/6 islets, an effect prevented by the antioxidant N-acetyl-L: -cysteine. Interestingly, while glutathione peroxidase and catalase expression was comparable between the two strains, the antioxidant enzyme manganese superoxide dismutase, which converts superoxide to hydrogen peroxide, was increased in DBA/2 islets, possibly explaining the increase in hydrogen peroxide levels.

CONCLUSIONS/INTERPRETATION: Chronic high glucose culture caused an impairment in glucose-stimulated insulin secretion in DBA/2 islets, which have a genetic predisposition to failure, and this may be the result of oxidative stress.

摘要

目的/假设:我们确定了高糖诱导的β细胞功能障碍是否与DBA/2小鼠(一种易发生胰岛功能衰竭的小鼠品系)的氧化应激有关。

材料与方法

将DBA/2小鼠和对照C57BL/6小鼠的胰岛暴露于高糖环境48小时后,测定葡萄糖和非葡萄糖介导的胰岛素分泌。通过测定O-糖基化蛋白水平评估己糖胺生物合成途径的通量。通过测量过氧化氢水平和抗氧化酶的表达来确定氧化应激。

结果

暴露于高糖水平会损害DBA/2胰岛而非C57BL/6胰岛的葡萄糖刺激的胰岛素分泌,这与胰岛胰岛素含量降低以及ATP水平低于C57BL/6胰岛有关。胰岛暴露于氨基葡萄糖48小时模拟了高糖对DBA/2胰岛胰岛素分泌的影响。高糖暴露会提高O-糖基化蛋白水平;然而,两个品系的胰岛中均出现这种情况,排除了O-糖基化在DBA/2胰岛素分泌受损中的作用。此外,氨基葡萄糖和高糖均导致DBA/2胰岛中的过氧化氢增加,但C57BL/6胰岛中未出现这种情况,抗氧化剂N-乙酰-L-半胱氨酸可阻止这种效应。有趣的是,虽然两个品系之间谷胱甘肽过氧化物酶和过氧化氢酶的表达相当,但将超氧化物转化为过氧化氢的抗氧化酶锰超氧化物歧化酶在DBA/2胰岛中增加,这可能解释了过氧化氢水平的升高。

结论/解读:慢性高糖培养导致具有功能衰竭遗传易感性的DBA/2胰岛中葡萄糖刺激的胰岛素分泌受损,这可能是氧化应激的结果。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验