Inhibition of Glucose-Induced Insulin Secretion by 4-Hydroxy-2-Nonenal and Other Lipid Peroxidation Products

I. Miwa
2000 Endocrinology  
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 M HNE for 1 h. Other lipid
more » ... ation products, e.g. 2-hexenal and 2-butenal, also inhibited glucose-induced insulin secretion. HNE at 100 M lowered ␣-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. (Endocrinology 141:
doi:10.1210/en.141.8.2767 pmid:10919261 fatcat:dzw24gxak5gzzihkfi56sybsky