Structural modifications of human albumin in diabetes.

AIM Albumin, a major protein in the blood circulation, can undergo increased glycation in diabetes. From recent studies, it has become evident that glycation has important implications for albumin actions and impact on cell functioning. This study compares the structural and functional properties of albumin glycated by glucose and methylglyoxal (MGO) with those of albumin purified from diabetic patients. METHODS Human serum albumin (HSA) was purified from diabetic patients and control subjects using affinity chromatography, and oxidation parameters in various albumin preparations were determined. Tryptophan and 1-anilino-8-naphthalene sulphonic acid (ANSA) probe fluorescence, redox state, antioxidant and copper-binding capacities of the different preparations of albumin were also determined and compared. RESULTS Occurrence of oxidative modifications was enhanced in albumin whether purified from diabetic patients, or glycated by glucose or MGO, after determination of their fructosamine and free thiol and amino group contents, carbonyl content and antioxidant activities. Whereas more quantitative changes in oxidative and structural parameters were observed in the glucose- and MGO-modified albumins, significant impairment of albumin function (free-radical-scavenging and copper-binding capacities) were demonstrated in the HSA purified from diabetics. These findings reveal different structural and functional features of diabetic HSA compared with in vitro models. CONCLUSION This study provides new information supporting albumin as an important biomarker for monitoring diabetic pathophysiology. In addition, it reconfirms the influence of experimental conditions in which advanced glycation end-products (AGEs) are generated in tests designed to mimic the pathological conditions of diabetes.