Characterisation of glyoxalase I in a streptozocin-induced mouse model of diabetes with painful and insensate neuropathy

• Published in: Diabetologia 2011-08, Vol.54 (8), p.2174-2182
• Main Authors: Jack, M. M., Ryals, J. M., Wright, D. E.
• Format: Article
• Language: English
• Subjects: Abundance; Age; Animal models; Animals; Biological and medical sciences; Blotting, Western; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - enzymology; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Diabetes. Impaired glucose tolerance; Diabetic Neuropathies - enzymology; Diabetic Neuropathies - genetics; Diabetic Neuropathies - metabolism; Diabetic neuropathy; Dorsal root ganglia; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzymes; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fluorescent Antibody Technique; Ganglia, Spinal - metabolism; Glucose; Human Physiology; Hyperglycemia; Immunofluorescence; Immunohistochemistry; Inbreeding; Internal Medicine; Lactoylglutathione lyase; Lactoylglutathione Lyase - genetics; Lactoylglutathione Lyase - metabolism; Male; Mechanical stimuli; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nervous system; Neurons; Neurotransmission; Pain; Peripheral Nervous System - metabolism; Peripheral neuropathy; Polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; Sensory neurons; Western blotting
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-011-2196-3

Aims/hypothesis Diabetic peripheral neuropathy (DN) is a common complication of diabetes; however, the mechanisms producing positive or negative symptoms are not well understood. The enzyme glyoxalase I (GLO1) detoxifies reactive dicarbonyls that form AGEs and may affect the way sensory neurons respond to heightened AGE levels in DN. We hypothesised that differential GLO1 levels in sensory neurons may lead to differences in AGE formation and modulate the phenotype of DN. Methods Inbred strains of mice were used to assess the variability of Glo1 expression by quantitative RT-PCR. Non-diabetic C57BL/6 mice were used to characterise the distribution of GLO1 in neural tissues by immunofluorescence. Behavioural assessments were conducted in diabetic A/J and C57BL/6 mice to determine mechanical sensitivity, and GLO1 abundance was determined by western blot. Results GLO1immunoreactivity was found throughout the nervous system, but selectively in small, unmyelinated peptidergic dorsal root ganglia (DRG) neurons that are involved in pain transmission. GLO1 protein was present at various levels in DRG from different inbred mice strains. Diabetic A/J and C57BL/6 mice, two mouse strains with different levels of GLO1, displayed dramatically different behavioural responses to mechanical stimuli. Diabetic C57BL/6 mice also had a reduced abundance of GLO1 following diabetes induction. Conclusions/interpretation These findings reveal that the abundance of GLO1 varies between different murine strains and within different sensory neuron populations. These differences could lead to different responses of sensory neurons to the toxic effects of hyperglycaemia and reactive dicarbonyls associated with diabetes.