title: Glucose-6-phosphate dehydrogenase activity and NADPH/NADP+ ratio in liver and pancreas are dependent on the severity of hyperglycemia in rat.
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.
authors.affiliation: Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS-México, México. mardiaz2001@yahoo.com
authors.forename: Margarita
authors.initials: M
authors.lastname: Díaz-Flores
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Ibáñez-Hernández
authors.forename: Rosa Elba
authors.initials: RE
authors.lastname: Galván
authors.forename: Margarita
authors.initials: M
authors.lastname: Gutiérrez
authors.forename: Genoveva
authors.initials: G
authors.lastname: Durán-Reyes
authors.forename: Rafael
authors.initials: R
authors.lastname: Medina-Navarro
authors.forename: Dalila
authors.initials: D
authors.lastname: Pascoe-Lira
authors.forename: Clara
authors.initials: C
authors.lastname: Ortega-Camarillo
authors.forename: Cecilia
authors.initials: C
authors.lastname: Vilar-Rojas
authors.forename: Miguel
authors.initials: M
authors.lastname: Cruz
authors.forename: Luis Arturo
authors.initials: LA
authors.lastname: Baiza-Gutman
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology; D008099:Liver / Q000201:enzymology*; D008297:Male; D009249:NADP / Q000378:metabolism*; D009929:Organ Size; D010084:Oxidation-Reduction; D010179:Pancreas / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D009249:NADP; D005954:Glucosephosphate Dehydrogenase; D005978:Glutathione