9/17/2004 NewsRxDiabetes - (NewsRx.com & NewsRx.net) -- Vitamin Eprotects against inhibition of insulin signaling by oxidized low-densitylipoprotein (LDL).

"Oxidative stress is involved in several pathological conditions,including diabetes. Reactive oxygen species (ROS) have been demonstratedto act as second messengers for several hormones and cytokines, includinginsulin (INS). The effect of Cu2+-oxidized LDL (CuLDL) on INS-inducedgeneration of ROS and on INS signaling was investigated on cultured humanfibroblasts. Intracellular ROS generation was observed either in CuLDL- orin INS-treated cells. Moreover, CuLDL and INS had an additive effect onROS formation in human fibroblasts," investigators in France report.

"CuLDL by itself increased the phosphorylation of ERK without affectingthe PKB/Akt phosphorylation," said Cecile Maziere at the Universite dePicardie Jules Verne and collaborators in France. "CuLDL also stimulatedthe DNA binding activities of the transcription factors APl and NFkappaB.However, CuLDL dose-dependently prevented the INS-signaling pathway, byinhibiting the INS-induced phosphorylation of the signaling kinases ERKand PKB/Akt and the INS-induced activation of the transcription factorsAPl and NFkappaB. Finally, the lipophilic antioxidant vitamin E (Vit E)partially restored all the studied signaling events initiated by INS andimpaired after pretreatment with CuLDL."

The researchers concluded, "These studies demonstrate that the oxidativestress generated by CuLDL has a negative effect on the INS-signalingpathway, independently of the INS-induced generation of ROS. Thus,oxidized LDL might be involved not only in atherosclerosis, as it iscommonly admitted, but also in the INS-resistance observed in type 2diabetes mellitus."

Maziere and associates published their study in Atherosclerosis(Inhibition of insulin signaling by oxidized low density lipoprotein.Protective effect of the antioxidant vitamin E. Atherosclerosis,2004;175(1):23-30).

For additional information, contact Cecile Maziere, Laboratoire deBiochimie EA 2087, CHU Amiens, Universite de Picardie Jules Verne, HopitalNord, Place Victor Pauchet, 80054 Amiens Cedex 1, France. E-mail:maziere.cecile@chu-amiens.fr.

The publisher of the journal Atherosclerosis can be contacted at: ElsevierScience Ireland Ltd., Customer Relations Manager, Bay 15, ShannonIndustrial Estate, Co. Clare, Clare, Ireland.

The information in this article comes under the major subject areas ofDiabetes Therapy, Diabetes Pathogenesis, Diabetes Complications, Type 2Diabetes, Endocrinology, Atherosclerosis, Lipid Studies, Reactive OxygenSpecies, and Proteomics.

This article was prepared by Diabetes Week editors from staff and otherreports.