Glyoxalase 1 and glyoxalase 2 activities in blood and neuronal tissue samples from experimental animal models of obesity and type 2 diabetes mellitus

Abstract

The glyoxalase enzymes catalyse the conversion of reactive glucose metabolites into non-toxic products as a part of the cellular defence system against glycation. This study investigated changes in glyoxalase 1 and glyoxalase 2 activities and the development of diabetic complications in experimental animal models of obesity (Zucker fa/fa rats) and type 2 diabetes mellitus (Goto-Kakizaki rats). In contrast to Zucker rats, in Goto-Kakizaki rats the glyoxalase 1 activities in brain, spinal cord and sciatic nerve tissues were significantly reduced by 10, 32 and 36 %, respectively. Lower glyoxalase 1 activity in the neuronal tissues was associated with a higher blood glucose concentration and impaired endothelium-dependent relaxation to acetylcholine in aortic rings in Goto-Kakizaki rats. This study provides evidence for disturbed neuronal glyoxalase 1 activity under conditions of hyperglycaemia in the presence of impaired endothelium-dependent relaxation and cognitive function.

Fig. 1

Plasma glucose (a) and triglycerides (b) concentrations in Wistar, Goto-Kakizaki, Zucker lean and Zucker fa/fa rats at 24 weeks of age. The data are presented as the mean ± SEM of at least 11 animals. *p < 0.05 compared to the Wistar control. ^# p < 0.05 compared to the Zucker lean control

Fig. 2

Glyoxalase 1 (Glo1) and glyoxalase 2 (Glo2) activities in blood. Changes in Glo1 and Glo2 activity in blood from Wistar, Goto-Kakizaki (a, b) and Zucker fa/fa and lean (c, d) rats from 8 to 24 weeks of age. The Glo1 activity in the whole blood lysates was defined as the μmol of S-d-lactoylglutathione formed per min per g of haemoglobin. The Glo2 activity in the whole blood lysates was defined as μmol of S-d-lactoylglutathione hydrolysed per min per g of haemoglobin. The data are presented as the mean ± SEM of at least 11 animals. *p < 0.05 compared to the control group, ^# p < 0.05 compared to 8 weeks in the respective group

Fig. 3

Glyoxalase 1 (Glo1) and glyoxalase 2 (Glo2) activities in neuronal tissues. Glo1 and Glo2 activity in the cortex, hypothalamus, spinal cord and sciatic nerve tissues from Wistar, Goto-Kakizaki (a, b) and Zucker fa/fa and lean (c, d) rats at 24 weeks of age. Non-diabetic rats (white bars), diabetic rats (black bars). The Glo1 activity in tissue homogenates was defined as the μmol of S-d-lactoylglutathione formed per min per g of protein. The Glo2 activity in tissue homogenates was defined as μmol of S-d-lactoylglutathione hydrolysed per min per g of protein. The data are presented as the mean ± SEM of at least 6 animals. *p < 0.05 compared to the control group

Fig. 4

Endothelium-dependent relaxation of isolated aortic rings in Wistar, Goto-Kakizaki, Zucker lean and Zucker fa/fa rats. Concentration–response curve of acetylcholine (10⁻¹⁰–10⁻⁵M) in isolated aortic rings of Wistar and Goto-Kakizaki (a) and Zucker lean and fa/fa (b) rats at 24 weeks of age. The data are presented as the mean % of relaxation ± SEM of at least 11 animals. *p < 0.05 compared to the control group

Fig. 5

Spontaneous alternation behaviour in Wistar, Goto-Kakizaki, Zucker lean and Zucker fa/fa rats. The spontaneous alternation behaviour in the Y-maze test in Wistar and Goto-Kakizaki (a) and Zucker lean and fa/fa (b) rats at 8, 16, and 24 weeks of age. Non-diabetic rats (white bars), diabetic rats (black bars). The data are presented as the mean % of alternation behaviour ± SEM of at least 11 animals. *p < 0.05 compared to the control group