Inhibition of glucose-induced insulin secretion by 4-hydroxy-2-nonenal and other lipid peroxidation products
Inhibition of glucose-induced insulin secretion by 4-hydroxy-2-nonenal and other lipid peroxidation products
复制标题
DOI：
10.1210/en.141.8.2767
复制
发表时间：
2000-08-01
期刊：
影响因子：
4.8
通讯作者：
Taniguchi, S
中科院分区：
文献类型：
--
作者：
Miwa, I;Ichimura, N;Taniguchi, S
在高血糖条件下，如糖尿病，由于氧化应激导致的脂质过氧化作用加速。本文观察了4-羟基-2-壬烯醛（HNE）等脂质过氧化产物对离体大鼠胰岛分泌胰岛素能力的影响。HNE浓度和时间依赖性地恶化葡萄糖诱导的胰岛素分泌：当用100 ELM HNE孵育胰岛1小时后测量时，胰岛素分泌减少50%。其他脂质过氧化产物，如2-己烯醛和2-丁烯醛，也抑制葡萄糖诱导的胰岛素分泌。HNE在100亩降低α-酮异己酸诱导的胰岛素分泌，而亮氨酸诱导的胰岛素分泌刺激。HNE可轻微降低10 mM甘油醛诱导的胰岛素分泌。另一方面，HNE严重降低由10 mM甘油醛和2.8 mM葡萄糖诱导的胰岛素分泌。葡萄糖利用和葡萄糖氧化显着降低与HNE处理的胰岛。用HNE处理后，胰岛中果糖1，6-二磷酸和二羟丙酮磷酸的含量减少，而果糖6-磷酸的含量增加。我们的研究表明，HNE和其他脂质过氧化产物可能通过影响糖酵解途径和柠檬酸循环来损害葡萄糖诱导的胰岛素分泌。
Lipid peroxidation due to oxidative stress is accelerated under hyperglycemic conditions such as diabetes mellitus. The effect of 4-hydroxy-2-nonenal (HNE) and other lipid peroxidation products on the ability of isolated rat pancreatic islets to secrete insulin was examined in this study. HNE concentration- and time-dependently deteriorated glucose-induced insulin secretion: insulin secretion was decreased by 50% when measured after incubation of islets with 100 ELM HNE for 1 h. Other lipid peroxidation products, e.g. 2-hexenal and 2-butenal, also inhibited glucose-induced insulin secretion. HNE at 100 mu lowered alpha-ketoisocaproate-induced insulin secretion, whereas leucine-induced insulin secretion was stimulated. Insulin secretion induced by 10 mM glyceraldehyde was slightly decreased by HNE. On the other hand, HNE severely decreased insulin secretion induced by 10 mM glyceraldehyde and 2.8 mM glucose. Glucose utilization and glucose oxidation were significantly lowered in islets treated with HNE. The amounts of fructose 1,6-bisphosphate and dihydroxyacetone phosphate in islets were decreased by treatment with HNE, whereas the amount of fructose 6-phosphate was increased. Our study indicates that HNE and other lipid peroxidation products impair insulin secretion induced by glucose probably through affecting both the glycolytic pathway and the citric acid cycle.