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doi:10.1016/j.lfs.2005.10.022 
Copyright © 2005 Elsevier Inc. All rights reserved.
Glucose-6-phosphate dehydrogenase activity and NADPH/NADP+ ratio in liver and pancreas are dependent on the severity of hyperglycemia in rat
Margarita Díaz-Floresa, c, 
, 
, Miguel Angel Ibáñez-Hernándezc, Rosa Elba Galvánb, Margarita Gutiérreza, Genoveva Durán-Reyesa, Rafael Medina-Navarroa, Dalila Pascoe-Liraa, Clara Ortega-Camarilloa, Cecilia Vilar-Rojasa, Miguel Cruza and Luis Arturo Baiza-Gutmand
Received 8 June 2005;
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Abstract
Hyperglycemia is associated with metabolic disturbances affecting cell redox potential, particularly the NADPH/NADP+ ratio and reduced glutathione levels. Under oxidative stress, the NADPH supply for reduced glutathione regeneration is dependent on glucose-6-phosphate dehydrogenase. We assessed the effect of different hyperglycemic conditions on enzymatic activities involved in glutathione regeneration (glucose-6-phosphate dehydrogenase and glutathione reductase), NADP(H) and reduced glutathione concentrations in order to analyze the relative role of these enzymes in the control of glutathione restoration. Male Sprague–Dawley rats with mild, moderate and severe hyperglycemia were obtained using different regimens of streptozotocin and nicotinamide. Fifteen days after treatment, rats were killed and enzymatic activities, NADP(H) and reduced glutathione were measured in liver and pancreas.
Severe hyperglycemia was associated with decreased body weight, plasma insulin, glucose-6-phosphate dehydrogenase activity, NADPH/NADP+ ratio and glutathione levels in the liver and pancreas, and enhanced NADP+ and glutathione reductase activity in the liver. Moderate hyperglycemia caused similar changes, although body weight and liver NADP+ concentration were not affected and pancreatic glutathione reductase activity decreased. Mild hyperglycemia was associated with a reduction in pancreatic glucose-6-phosphate dehydrogenase activity. Glucose-6-phosphate dehydrogenase, NADPH/NADP+ ratio and glutathione level, vary inversely in relation to blood glucose concentrations, whereas liver glutathione reductase was enhanced during severe hyperglycemia. We conclude that glucose-6-phosphate dehydrogenase and NADPH/NADP+ were highly sensitive to low levels of hyperglycemia. NADPH/NADP+ is regulated by glucose-6-phosphate dehydrogenase in the liver and pancreas, whereas levels of reduced glutathione are mainly dependent on the NADPH supply.
Keywords: Oxidative stress; Glucose-6-phosphate dehydrogenase; Glutathione; Glutathione reductase; NADPH/NADP+ ratio; Experimental diabetes
Article Outline
- Introduction
- Materials and methods
- Materials
- Animals and drug treatment
- Tissue preparation
- Assessment of glucose and insulin
- Enzyme activity assay
- Determination of pyridine nucleotide phosphates
- Measurement of GSH
- Statistical analysis
- Results
- General characteristics of treated animals
- Differential response of G6PDH and GR to hyperglycemia
- GSH level and NADPH/NADP+ ratio decreased by hyperglycemia
- Discussion
- Acknowledgements
- References
