Prior cadmium exposure improves glucoregulation in diabetic rats but exacerbates effects on metabolic dysregulation, oxidative stress, and hepatic and renal toxicity

Abstract

The present study was taken up to assess the role of subchronic exposure to an environmentally relevant dosage of cadmium in type l diabetes. Female rats of the Wistar strain were treated with cadmium (5.12 mg/kg body weight) for 45 days. On day 46, rats were made diabetic by alloxan. After 7 days, diabetes (i.e., animals with serum glucose greater than 300 mg/dL) in the alloxanized animals was confirmed and further experiments were conducted for 15 days. Cadmium pretreatment showed disturbed glucose homeostasis with attendant changes in carbohydrate metabolism, coupled with decrease in food and water intake. Disturbance in carbohydrate metabolism was indicated by altered tissue metabolite load, as marked by a decrease in protein and glycogen contents and increased cholesterol store. Poor glucose clearance subsequent to a glucose challenge under the glucose tolerance test was observed in these animals (0.48/min in control vs. 0.13/min in Cd animals). There was a significantly lower glucose elevation rate in the insulin response test subsequent to an insulin-induced decrease in glucose level in Cd-exposed animals. Elevated oxidative stress was marked by increased lipid peroxidation, decreased antioxidant (both nonenzymatic and enzymatic) levels, and serum markers of hepatic and renal damage. Decreased corticosterone levels, together with increased E2 and reduced P4 levels, were some of the hallmark changes in the serum hormone profile of Cd-exposed animals. Overall, the present results are novel and interesting to open more investigations on animal models of type 1 diabetes with a history of previous Cd exposure.