title: Alpha-lipoic acid treatment reverses 2-deoxy-D-ribose-induced oxidative damage and suppression of insulin expression in pancreatic beta-cells.
abstract: We investigated whether α-lipoic acid (LA) could prevent 2-deoxy-D-ribose (dRib)-induced oxidative damage and suppression of insulin expression in pancreatic β-cells. Stimulation with 50 mM dRib elevated cytotoxicity, apoptosis and intracellular reactive oxygen species (ROS) levels in HIT-T15 cells, but pretreatment with LA significantly reversed the dRib-induced changes. LA directly scavenged hydroxyl radicals generated by a Fenton reaction. Intracellular reduced glutathione (GSH) and oxidized glutathione (GSSG) were depleted by stimulation with dRib but levels were restored by addition of LA to HIT-T15 cells. However, the GSH/GSSG ratio was unchanged by LA treatment. In rat islets, stimulation with 10 mM dRib for 6 h suppressed expression of insulin and pancreatic and duodenal homeobox 1 mRNA and decreased insulin content, but these were dose-dependently reversed when LA was added. Treatment with l-buthionine-sulfoximine, an inhibitor of intracellular glutathione biosynthesis, completely abolished the protective effects of LA on dRib-mediated glutathione depletion and cytotoxicity in HIT-T15 cells. In summary, LA reversed the dRib-induced oxidative damage and suppression of insulin expression in β-cells. Enhanced intracellular total glutathione production, rather than the scavenging of ROS, is possibly the mechanism for the protective effect of LA.
authors.affiliation: Department of Internal Medicine, Jeju National University School of Medicine.
authors.forename: Gwanpyo
authors.initials: G
authors.lastname: Koh
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Yang
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Sang Ah
authors.initials: SA
authors.lastname: Lee
authors.forename: Dae-Ho
authors.initials: DH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D003855:Deoxyribose / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000009:adverse effects; D005978:Glutathione / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D018398:Homeodomain Proteins; D007328:Insulin; D012333:RNA, Messenger; D019328:Buthionine Sulfoximine; D003855:Deoxyribose; D008063:Thioctic Acid; D005978:Glutathione; D005947:Glucose