Modelling the effects of elevated methylglyoxal levels on vascular and metabolic complications

Philippe Vangrieken*, Jean L.J.M. Scheijen, Paul M.H. Schiffers, Marjo P.H. van de Waarenburg, Sebastien Foulquier, Casper C.G. Schalkwijk

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Methylglyoxal (MGO), a glycolysis by-product and precursor to advanced glycation endproducts (AGEs), is associated with glucose intolerance, type 2 diabetes, and vascular dysfunction. This study examined the long-term effects of elevated MGO on blood pressure, insulin sensitivity, and vascular function in healthy mice. Male C57Bl/6J mice were assigned to control (n = 16) or MGO-treated groups (50 mM in drinking water for 13 weeks, n = 16). Measurements included body weight, fasting plasma glucose, water consumption, blood pressure, and analysis of plasma/tissue for MGO, AGEs, glyoxalase activity, and inflammation markers. Endothelial function was assessed using wire myography, and the response of human placental arteries to MGO-modified insulin was evaluated. MGO treatment significantly increased plasma MGO (123.3%, p < 0.001), AGEs MG-H1 (208.6%, p < 0.001) and CEL (64.3%, p < 0.001), and AGEs in the heart, kidney, and liver, along with body weight (+ 6.4%, p = 0.032) and blood pressure (systolic + 5.0%, p = 0.046; diastolic + 6.5%, p = 0.043). Glucose sensitivity and endothelial function remained unaffected. CRP levels rose, and MGO-modified insulin enhanced vascular contraction. In conclusion, chronic MGO exposure increased plasma MGO to diabetic-like levels, raised body weight and blood pressure, and did not alter glucose sensitivity or endothelial function. Modification of insulin by MGO may contribute to MGO-related changes in blood pressure.
Original languageEnglish
Article number6025
Number of pages15
JournalScientific Reports
Volume15
Issue number1
DOIs
Publication statusPublished - 19 Feb 2025

Keywords

  • Advanced glycation endproducts
  • Diabetes
  • Hypertension
  • Insulin resistance
  • Metabolic toxicity
  • Methylglyoxal

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