Modelling the effects of elevated methylglyoxal levels on vascular and metabolic complications
Philippe Vangrieken, Jean L.J.M. Scheijen, Paul Schiffers, Marjo P. H. van de Waarenburg, Sébastien Foulquier, Casper G. Schalkwijk
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.