Diabetes and dietary copper alter 67Cu metabolism and oxidant defense in the rat.
Perturbations in copper (Cu) metabolism are a characteristic of diabetes, for example, elevated plasma Cu and compromised oxidant defense related to diabetes-induced effects on Cu-containing enzymes. Herein, the redistribution of Cu in selected tissues is described in response to diabetic and nondiabetic states in rats that were fed diets adequate in (12 mg Cu/kg of diet) or deficient in (no added Cu) Cu. Diabetes was induced by intravenous administration of streptozotocin (40 mg/kg body weight). After 5 weeks, rats were gavaged with (67)Cu (0.74 MBq per rat) using the Cu-deficient diet as a vehicle (suspended 1:3 in water) and killed at various time points. The use of (67)Cu allowed for the assessment of short-term Cu distribution and its comparison to the steady-state Cu distribution, as determined by direct Cu analysis. In contrast to control rats, the adaptive mechanisms for Cu homeostasis in diabetic rats were impaired. In general, measures of Cu retention were reduced in diabetic rats compared to corresponding values for control rats. Moreover, diabetic rats had low copper, zinc superoxide dismutase activity that was reduced even further when diabetic rats were fed with low-Cu diets. However, liver and kidney metallothionein and plasma ceruloplasmin levels were elevated in diabetic rats compared to control rats. Such diabetes-related metabolic alterations were taken as measures of increased oxidative stress and inflammation, which may have implications in the progression of diabetes-related pathologies.
Uriu-Adams
Janet Y
JY
Department of Nutrition, University of California at Davis, Davis, CA 95616-8669, USA. jyuriuadams@ucdavis.edu
Rucker
Robert B
RB
Commisso
Joel F
JF
Keen
Carl L
CL
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000172:deficiency / Q000378:metabolism*; D003301:Copper Radioisotopes; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008668:Metallothionein / Q000378:metabolism; D016877:Oxidants / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014018:Tissue Distribution
D003301:Copper Radioisotopes; D016877:Oxidants; D003300:Copper; D008668:Metallothionein; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D002570:Ceruloplasmin; D005980:Glutathione Reductase