title: Glutathione synthesis by red blood cells in type 2 diabetes mellitus.
abstract: Oxidative stress is implicated in the pathogenesis and complications of type 2 diabetes mellitus (NIDDM). Glycoxidation may damage the enzymes that synthesise glutathione (GSH), an endogenous intracellular antioxidant. Erythrocytes (RBCs) taken from NIDDM subjects, and non-diabetic controls, were GSH-depleted using 1-chloro-2,4-dinitrobenzene, incubated in a solution containing GSH-rebuilding substrates, and sampled for GSH using a 5,5'-gamma-dithiobis-(2-nitrobenzoic acid)/enzymatic recycling procedure. NIDDM subjects, on average, had the same GSH concentration and synthesising ability as non-diabetic controls, indicating normal function of the synthesis enzymes. A positive correlation between synthesis and concentration of GSH seen in non-diabetic controls did not exist in NIDDM, due to their putatively larger oxidative load. The results, to the best of our knowledge, provide the first evidence that, despite a higher oxidative load, intact RBCs from NIDDM subjects are able to synthesise GSH normally. It is hypothesised that increased rates of GSH synthesis would maintain a normal steady-state GSH concentration.
authors.affiliation: Department of Biological Sciences, Macquarie University, Sydney, New South Wales, Australia. swhillier@bio.mq.edu.au
authors.forename: Stephney
authors.initials: S
authors.lastname: Whillier
authors.forename: Julia Elizabeth
authors.initials: JE
authors.lastname: Raftos
authors.forename: Philip William
authors.initials: PW
authors.lastname: Kuchel
mesh_terms: D000328:Adult; D000367:Age Factors; D000975:Antioxidants / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000096:biosynthesis* / Q000097:blood*; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000097:blood
chemical_list: D000975:Antioxidants; D005978:Glutathione; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species