Multi-targeted mechanisms underlying the endothelial protective effects of the diabetic-safe sweetener erythritol

Diabetes is characterized by hyperglycemia and development of vascular Endothelial cell dysfunction is a starting point for pathogenesis of complications in diabetes. We previously showed the polyol erythritol to hydroxyl radical scavenger preventing endothelial cell dysfunction onset diabetic rats. To unravel mechanisms, other than scavenging of radicals, erythritol mediates this protective effect, we evaluated effects of endothelial cells exposed to normal (7 mM) and high glucose (30 mM) or stressors (e.g. SIN-1) using targeted and transcriptomic approaches. demonstrates that erythritol (i.e. under non-diabetic conditions) has effects on endothelial cells. However, under hyperglycemic conditions protected endothelial cells against cell death induced by diabetic (i.e. high glucose and peroxynitrite). Also a number of harmful effects high glucose, e.g. increased nitric oxide release, are reversed. total transcriptome analysis indicated that biological processes which differentially regulated due to high glucose are corrected by conclude that erythritol protects endothelial cells during high glucose conditions via effects on multiple targets. Overall, these data indicate therapeutically important endothelial protective effect of erythritol hyperglycemic conditions.