An Increased Osteoprotegerin Serum Release Characterizes the Early Onset of Diabetes Mellitus and May Contribute to Endothelial Cell Dysfunction

摘要: Serum osteoprotegerin (OPG) is significantly increased in diabetic patients, prompting expanded investigation of the correlation between OPG production/release and glycemic levels. levels OPG, but not its cognate ligand receptor activator nuclear factor-κB (RANKL), were type 2 diabetes mellitus patients compared with healthy blood donors. was also elevated a subgroup recently diagnosed (within years). The relationship serum onset next investigated apoE-null littermate mice. early after induction both mouse strains showed positive glucose an inverse free (OPG-unbound) RANKL. vitro addition tumor necrosis factor-α to human vascular endothelial cells, peripheral mononuclear markedly enhanced release culture. In contrast, high concentrations did modulate when used alone or association factor-α. Moreover, ability soluble RANKL activate extracellular signal-regulated kinase/mitogen-activated protein kinase nitric-oxide synthase pathways cells neutralized by preincubation recombinant OPG. Altogether, these findings suggest that production represents event natural history mellitus, possibly contributing disease-associated cell dysfunction.