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

Diabetes is characterized by hyperglycemia and development of vascular pathology. Endothelial cell dysfunction is a starting point for pathogenesis of vascular complications in diabetes. We previously showed the polyol erythritol to be a hydroxyl radical scavenger preventing endothelial cell dysfunc...

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Published in:PloS one 2013-06, Vol.8 (6), p.e65741
Main Authors: Boesten, Daniëlle M P H J, Berger, Alvin, de Cock, Peter, Dong, Hua, Hammock, Bruce D, den Hartog, Gertjan J M, Bast, Aalt
Format: Article
Language:English
Subjects:
Acids
Analysis
Biological activity
Biology
Cell death
Cell Death - drug effects
Cell Survival - drug effects
Cells, Cultured
Complications
Cytoprotection
Deoxyguanosine - analogs & derivatives
Deoxyguanosine - metabolism
Diabetes
Diabetes mellitus
Drug Evaluation, Preclinical
Eicosanoids - metabolism
Endothelial cells
Endothelium
Erythritol
Erythritol - pharmacology
Gene expression
Glucose
Glucose - pharmacology
Glucose - physiology
Human Umbilical Vein Endothelial Cells - drug effects
Human Umbilical Vein Endothelial Cells - physiology
Humans
Hydroxyl radicals
Hyperglycemia
Hyperglycemia - metabolism
Kinases
Medicine
Natural language processing
Nitric oxide
Oxidative Stress
Pathogenesis
Penicillin
Peroxynitrite
Polyols
Proteins
Rats
Rodents
Sweetening Agents - pharmacology
Toxicology
Transcriptome - drug effects
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cited_by cdi_FETCH-LOGICAL-c692t-daff9ba86ca5650c3634519fd8ed54365aa6cb39a14ebb418a6c1f261d0b7b13
cites cdi_FETCH-LOGICAL-c692t-daff9ba86ca5650c3634519fd8ed54365aa6cb39a14ebb418a6c1f261d0b7b13
container_end_page
container_issue 6
container_start_page e65741
container_title PloS one
container_volume 8
creator Boesten, Daniëlle M P H J
Berger, Alvin
de Cock, Peter
Dong, Hua
Hammock, Bruce D
den Hartog, Gertjan J M
Bast, Aalt
description Diabetes is characterized by hyperglycemia and development of vascular pathology. Endothelial cell dysfunction is a starting point for pathogenesis of vascular complications in diabetes. We previously showed the polyol erythritol to be a hydroxyl radical scavenger preventing endothelial cell dysfunction onset in diabetic rats. To unravel mechanisms, other than scavenging of radicals, by which erythritol mediates this protective effect, we evaluated effects of erythritol in endothelial cells exposed to normal (7 mM) and high glucose (30 mM) or diabetic stressors (e.g. SIN-1) using targeted and transcriptomic approaches. This study demonstrates that erythritol (i.e. under non-diabetic conditions) has minimal effects on endothelial cells. However, under hyperglycemic conditions erythritol protected endothelial cells against cell death induced by diabetic stressors (i.e. high glucose and peroxynitrite). Also a number of harmful effects caused by high glucose, e.g. increased nitric oxide release, are reversed. Additionally, total transcriptome analysis indicated that biological processes which are differentially regulated due to high glucose are corrected by erythritol. We conclude that erythritol protects endothelial cells during high glucose conditions via effects on multiple targets. Overall, these data indicate a therapeutically important endothelial protective effect of erythritol under hyperglycemic conditions.
doi_str_mv 10.1371/journal.pone.0065741
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Additionally, total transcriptome analysis indicated that biological processes which are differentially regulated due to high glucose are corrected by erythritol. We conclude that erythritol protects endothelial cells during high glucose conditions via effects on multiple targets. Overall, these data indicate a therapeutically important endothelial protective effect of erythritol under hyperglycemic conditions.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23755276</pmid><doi>10.1371/journal.pone.0065741</doi><tpages>e65741</tpages><oa>free_for_read</oa></addata></record>
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subjects Acids
Analysis
Biological activity
Biology
Cell death
Cell Death - drug effects
Cell Survival - drug effects
Cells, Cultured
Complications
Cytoprotection
Deoxyguanosine - analogs & derivatives
Deoxyguanosine - metabolism
Diabetes
Diabetes mellitus
Drug Evaluation, Preclinical
Eicosanoids - metabolism
Endothelial cells
Endothelium
Erythritol
Erythritol - pharmacology
Gene expression
Glucose
Glucose - pharmacology
Glucose - physiology
Human Umbilical Vein Endothelial Cells - drug effects
Human Umbilical Vein Endothelial Cells - physiology
Humans
Hydroxyl radicals
Hyperglycemia
Hyperglycemia - metabolism
Kinases
Medicine
Natural language processing
Nitric oxide
Oxidative Stress
Pathogenesis
Penicillin
Peroxynitrite
Polyols
Proteins
Rats
Rodents
Sweetening Agents - pharmacology
Toxicology
Transcriptome - drug effects
title Multi-targeted mechanisms underlying the endothelial protective effects of the diabetic-safe sweetener erythritol
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