ArticleDiabetologia2014
Methylglyoxal impairs endothelial insulin sensitivity both in vitro and in vivo.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 79 citations in OpenAlex.
- Beyond hyperglycaemia: diabetic retinopathy is a multifactorial complication of diabetes mellitus.Annals of medicine · 2026Review
- Brazilin attenuates methylglyoxal‑induced endothelial injury by enhancing eIF5A hypusination and inhibiting the AMPK/mTOR‑mediated autophagy/apoptosis axisInternational journal of molecular medicine · 2026Article
- Exploration and analysis of methylglyoxal-driven chronic inflammation in polycystic ovary syndrome.Journal of advanced research · 2026Article
- Higher intake of dietary dicarbonyl compounds is associated with lower incidence of type 2 diabetes: European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study.European journal of nutrition · 2026Article
- Effects of sourdough and yeast fermented breads consumption on glycaemia in healthy populations: a systematic review.Frontiers in nutrition · 2026Review
- Does Gut Microbial Methylglyoxal Metabolism Impact Human Physiology?Antioxidants (Basel, Switzerland) · 2025Review
- A Comprehensive Review of Metabolic Dysfunction-Associated Steatotic Liver Disease: Its Mechanistic Development Focusing on Methylglyoxal and Counterbalancing Treatment Strategies.International journal of molecular sciences · 2025Review
- Modelling the effects of elevated methylglyoxal levels on vascular and metabolic complications.Scientific reports · 2025Article
- Loss of NAMPT and SIRT2 but not SIRT1 attenuate GLO1 expression and activity in human skeletal muscle.Redox biology · 2024Article
- LCZ696, an Angiotensin Receptor-Neprilysin Inhibitor, Ameliorates Endothelial Dysfunction in Diabetic C57BL/6 Mice.Journal of atherosclerosis and thrombosis · 2024Article
- Protein glycation products associate with progression of kidney disease and incident cardiovascular events in individuals with type 1 diabetes.Cardiovascular diabetology · 2024Article
- Methylglyoxal in Cardiometabolic Disorders: Routes Leading to Pathology Counterbalanced by Treatment Strategies.Molecules (Basel, Switzerland) · 2023Review
- Glyoxalase I is a novel target for the prevention of metabolic derangement.Pharmacology & therapeutics · 2023Review
- Article
- Blood and Tissue Advanced Glycation End Products as Determinants of Cardiometabolic Disorders Focusing on Human Studies.Nutrients · 2023Review
- Habitual intake of dietary methylglyoxal is associated with less low-grade inflammation: the Maastricht Study.The American journal of clinical nutrition · 2022Article
- RAGE displays sex-specific differences in obesity-induced adipose tissue insulin resistance.Biology of sex differences · 2022Article
- Glyoxalase 1 knockdown induces age-related β-cell dysfunction and glucose intolerance in mice.EMBO reports · 2022Article
- Metformin prevents methylglyoxal-induced apoptosis by suppressing oxidative stress in vitro and in vivo.Cell death & disease · 2022Article
- Methylglyoxal Scavengers Attenuate Angiogenesis Dysfunction Induced by Methylglyoxal and Oxygen-Glucose Deprivation.Oxidative medicine and cellular longevity · 2022Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisInsulin exerts a direct action on vascular cells, thereby affecting the outcome and progression of diabetic vascular complications. However, the mechanism through which insulin signalling is impaired in the endothelium of diabetic individuals remains unclear. In this work, we have evaluated the role of the AGE precursor methylglyoxal (MGO) in generating endothelial insulin resistance both in cells and in animal models.
methodsTime course experiments were performed on mouse aortic endothelial cells (MAECs) incubated with 500 μmol/l MGO. The glyoxalase-1 inhibitor S-p-bromobenzylglutathione-cyclopentyl-diester (SpBrBzGSHCp2) was used to increase the endogenous levels of MGO. For the in vivo study, an MGO solution was administrated i.p. to C57BL/6 mice for 7 weeks.
resultsMGO prevented the insulin-dependent activation of the IRS1/protein kinase Akt/endothelial nitric oxide synthase (eNOS) pathway, thereby blunting nitric oxide (NO) production, while extracellular signal-regulated kinase (ERK1/2) activation and endothelin-1 (ET-1) release were increased by MGO in MAECs. Similar results were obtained in MAECs treated with SpBrBzGSHCp2. In MGO- and SpBrBzGSHCp2-exposed cells, inhibition of ERK1/2 decreased IRS1 phosphorylation on S616 and rescued insulin-dependent Akt activation and NO generation, indicating that MGO inhibition of the IRS1/Akt/eNOS pathway is mediated, at least in part, by ERK1/2. Chronic administration of MGO to C57BL/6 mice impaired whole-body insulin sensitivity and induced endothelial insulin resistance. CONCLUSIONS/
interpretationMGO impairs the action of insulin on the endothelium both in vitro and in vivo, at least in part through an ERK1/2-mediated mechanism. These findings may be instrumental in developing novel strategies for preserving endothelial function in diabetes.
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