Inhibition of glucose-induced insulin secretion by 4-hydroxy-2-nonenal andother lipid peroxidation products

Lipid peroxidation due to oxidative stress is accelerated under hyperglycem ic 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 concen tration- and time-dependently deteriorated glucose-induced insulin secretio n: 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. H NE at 100 mu lowered alpha-ketoisocaproate-induced insulin secretion, where as leucine-induced insulin secretion was stimulated. Insulin secretion indu ced by 10 mM glyceraldehyde was slightly decreased by HNE. On the other han d, HNE severely decreased insulin secretion induced by 10 mM glyceraldehyde and 2.8 mM glucose. Glucose utilization and glucose oxidation were signifi cantly lowered in islets treated with HNE. The amounts of fructose 1,6-bisp hosphate and dihydroxyacetone phosphate in islets were decreased by treatme nt with HNE, whereas the amount of fructose 6-phosphate was increased. Our study indicates that HNE and other lipid peroxidation products impair insul in secretion induced by glucose probably through affecting both the glycoly tic pathway and the citric acid cycle.