Effects of Acute Experimental Hyperglycemia on Oxidative Markers and AGE-RAGE Dynamics in Obese Humans

Chronic hyperglycemia promotes oxidative stress and advanced glycation end product (AGE) formation, leading to recognition by the AGE receptor (RAGE). AGE-RAGE binding and inflammation perpetuates diabetic complications, however the study of these phenomenon present inherent challenges in vivo. Therefore, our purpose was to evaluate the effects of acute experimental hyperglycemia on AGEs, oxidative markers, and RAGE expression in healthy, obese subjects (n=10; 31.2±1.2 kg/m2; 56±3 y) subjected to hyperglycemic clamps (+5.4 mM above basal). Plasma was assayed at baseline, 2, and 24 h post glucose-infusion for well-known AGE-free adducts (CML, CEL, G-H1, MG-H1, 3DG-H) and oxidative markers (MethSO, AAA) via LC-MS/MS as well as soluble RAGE (sRAGE) isoforms via ELISA. Urine was also assayed (basal and 24 h) for AGEs and oxidative markers (normalized to creatinine) and skeletal muscle biopsies were used to study RAGE expression via Western blot. Most circulating factors (MethSO, AAA, CEL, MG-H1, and G-H1) decreased (p0.05). In urine, only MethSO was seen to increase at 24 h (p0.05). In skeletal muscle tissue, there was a trend (p Disclosure R. Perkins: None. E.R. Miranda: None. K. Karstoft: None. P.J. Beisswenger: Employee; Self; PreventAGE Health Care, LLC.. T.P. Solomon: None. J.M. Haus: None.