This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miwa, I. Articles by Taniguchi, S. Search for Related Content PubMed PubMed Citation Articles by Miwa, I. Articles by Taniguchi, S.

Inhibition of Glucose-Induced Insulin Secretion by 4-Hydroxy-2-Nonenal and Other Lipid Peroxidation Products¹

Departments of Pathobiochemistry (I.M., N.I., S.T.) and Organic Manufacturing (M.S., Y.H.), Faculty of Pharmacy, Meijo University, Nagoya 468-8503, Japan

Address all correspondence and requests for reprints to: Ichitomo Miwa, Ph.D., Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Tempaku-ku, Nagoya 468-8503, Japan. E-mail: miwaichi{at}meijo-u.ac.jp

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 µM HNE for 1 h. Other lipid peroxidation products, e.g. 2-hexenal and 2-butenal, also inhibited glucose-induced insulin secretion. HNE at 100 µM 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.

This article has been cited by other articles:

				D. Demozay, J.-C. Mas, S. Rocchi, and E. Van Obberghen FALDH Reverses the Deleterious Action of Oxidative Stress Induced by Lipid Peroxidation Product 4-Hydroxynonenal on Insulin Signaling in 3T3-L1 Adipocytes Diabetes, May 1, 2008; 57(5): 1216 - 1226. [Abstract] [Full Text] [PDF]

				A. I. Oprescu, G. Bikopoulos, A. Naassan, E. M. Allister, C. Tang, E. Park, H. Uchino, G. F. Lewis, I. G. Fantus, M. Rozakis-Adcock, et al. Free Fatty Acid Induced Reduction in Glucose-Stimulated Insulin Secretion: Evidence for a Role of Oxidative Stress In Vitro and In Vivo Diabetes, December 1, 2007; 56(12): 2927 - 2937. [Abstract] [Full Text] [PDF]

				C. Tang, P. Han, A. I. Oprescu, S. C. Lee, A. V. Gyulkhandanyan, G. N.Y. Chan, M. B. Wheeler, and A. Giacca Evidence for a Role of Superoxide Generation in Glucose-Induced {beta}-Cell Dysfunction In Vivo Diabetes, November 1, 2007; 56(11): 2722 - 2731. [Abstract] [Full Text] [PDF]

				S. N. A. Hussain, G. Matar, E. Barreiro, M. Florian, M. Divangahi, and T. Vassilakopoulos Modifications of proteins by 4-hydroxy-2-nonenal in the ventilatory muscles of rats Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L996 - L1003. [Abstract] [Full Text] [PDF]

				T. B. Mysore, T. A. Shinkel, J. Collins, E. J. Salvaris, N. Fisicaro, L. J. Murray-Segal, L. E.A. Johnson, D. A. Lepore, S. N. Walters, R. Stokes, et al. Overexpression of Glutathione Peroxidase With Two Isoforms of Superoxide Dismutase Protects Mouse Islets From Oxidative Injury and Improves Islet Graft Function Diabetes, July 1, 2005; 54(7): 2109 - 2116. [Abstract] [Full Text] [PDF]

				M. J. MacDonald, R. D. Husain, S. Hoffmann-Benning, and T. R. Baker Immunochemical Identification of Coenzyme Q0-Dihydrolipoamide Adducts in the E2 Components of the {alpha}-Ketoglutarate and Pyruvate Dehydrogenase Complexes Partially Explains the Cellular Toxicity of Coenzyme Q0 J. Biol. Chem., June 25, 2004; 279(26): 27278 - 27285. [Abstract] [Full Text] [PDF]

				J. L. Evans, I. D. Goldfine, B. A. Maddux, and G. M. Grodsky Are Oxidative Stress-Activated Signaling Pathways Mediators of Insulin Resistance and {beta}-Cell Dysfunction? Diabetes, January 1, 2003; 52(1): 1 - 8. [Abstract] [Full Text] [PDF]

				J. L. Evans, I. D. Goldfine, B. A. Maddux, and G. M. Grodsky Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes Endocr. Rev., October 1, 2002; 23(5): 599 - 622. [Abstract] [Full Text] [PDF]

				S. Deakin, I. Leviev, V. Nicaud, M.-C. B. Meynet, L. Tiret, and R. W. James Paraoxonase-1 L55M Polymorphism Is Associated with an Abnormal Oral Glucose Tolerance Test and Differentiates High Risk Coronary Disease Families J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1268 - 1273. [Abstract] [Full Text] [PDF]