TY - JOUR
T1 - Modelling the effects of elevated methylglyoxal levels on vascular and metabolic complications
AU - Vangrieken, Philippe
AU - Scheijen, Jean L.J.M.
AU - Schiffers, Paul M.H.
AU - van de Waarenburg, Marjo P.H.
AU - Foulquier, Sebastien
AU - Schalkwijk, Casper C.G.
N1 - Funding Information:
This project received funding from the PPP Allowance made available by Health\u223CHolland, Top Sector Life Sciences & Health, to stimulate public\u2013private partnerships under the umbrella of the European Joint Programming Initiative \u201CA Healthy Diet for a Healthy Life\u201D (JPI HDHL) and of the ERA-NET Cofund HDHL-INTIMIC (GA N\u00B0727565 of the EU Horizon 2020 Research and Innovation Programme and is supported by a fellowship from the Dutch Diabetes Research Foundation (Grant No. 2021.81.005). Funded by the Dutch Organisation for knowledge and innovation in health, healthcare and well-being (ZonMw): 01142042310002.
Publisher Copyright:
© The Author(s) 2025.
PY - 2025/2/19
Y1 - 2025/2/19
N2 - 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.
AB - 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.
KW - Advanced glycation endproducts
KW - Diabetes
KW - Hypertension
KW - Insulin resistance
KW - Metabolic toxicity
KW - Methylglyoxal
U2 - 10.1038/s41598-025-90661-5
DO - 10.1038/s41598-025-90661-5
M3 - Article
SN - 2045-2322
VL - 15
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 6025
ER -