High glucose causes vascular dysfunction through Akt/eNOS pathway: reciprocal modulation by juglone and resveratrol

Can J Physiol Pharmacol. 2018 Aug;96(8):757-764. doi: 10.1139/cjpp-2017-0639. Epub 2018 Mar 10.


Transient elevations in blood glucose level may lead to changes in vascular function. Herein, we investigated the effects of high-glucose or high-fructose challenge, as well as potential influence of juglone or resveratrol on vascular reactivity, Akt/eNOS, and insulin signaling effectors in rat aorta. Aortic segments of rats were incubated with high glucose (30 mmol/L) or high fructose (2 mmol/L) in the absence and presence of juglone (5 μmol/L) or resveratrol (10 μmol/L). Acute high-glucose incubation markedly decreased acetylcholine-induced relaxation, which is further inhibited by juglone, but ameliorated by resveratrol. Incubation with high glucose caused significant reduction in pAkt/total Akt and peNOS/total eNOS ratios, as well as in the expression of some genes involved in insulin signaling. Juglone produced a further impairment, whereas resveratrol resulted in an improvement on the expression profiles of these proteins and genes. Acute exposure of aortic segments to high glucose causes a reduction in acetylcholine-induced relaxation in association with suppression of Akt/eNOS pathway, as well as several genes in insulin signaling pathway. Juglone and resveratrol have opposite actions on vascular relaxation and the above signaling targets. These findings could be relevant for the treatment of hyperglycemia-induced vascular complications.

Keywords: Akt/eNOS pathway; concentrations élevées de glucose; fonction vasculaire; high glucose; juglone; resveratrol; resvératrol; vascular function; voie de signalisation Akt/eNOS.

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Aorta / drug effects
  • Aorta / metabolism*
  • Aorta / pathology
  • Aorta / physiopathology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology
  • Fructose / toxicity
  • Gene Expression Regulation / drug effects
  • Glucose / toxicity*
  • In Vitro Techniques
  • Male
  • Naphthoquinones / pharmacology*
  • Nitric Oxide Synthase Type III / metabolism*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats, Wistar
  • Resveratrol
  • Signal Transduction* / drug effects
  • Stilbenes / pharmacology*
  • Vasodilation / drug effects


  • Naphthoquinones
  • Stilbenes
  • Fructose
  • Nitric Oxide Synthase Type III
  • Proto-Oncogene Proteins c-akt
  • Glucose
  • Acetylcholine
  • Resveratrol
  • juglone