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.

Cadmium exposure decreases fasting blood glucose levels and exacerbates type-2 diabetes in a mouse model

“…This is in contrast with some published studies where Cd was reported to increase FBG levels in normal mice or diabetic mice [20,21]. However, our data were consistent with other studies showing that Cd decreased FBG levels [22,23]. The reasons for this discrepancy, and the anomaly of FBG and insulin both decreasing, are unclear.…”

Heavy Metal Exposure and Metabolic Syndrome: Evidence from Human and Model System Studies

“…Experimental studies using adult animals and cell culture models of Cd exposure have shown Cd to have both diabetogenic and antiobesogenic effects (Table 2). Adult female rats (180 days) exposed to high levels of Cd (3.1 ppm) via daily oral gavage for 45 days exhibited hyperglycemia, reduced serum insulin, progesterone and low density lipoproteins (LDL); increased serum estradiol, TGs, very low density lipoproteins (VLDL), and high density lipoproteins (HDL); and reduced glucose clearance at the end of treatment(42). Liver and muscle tissue was harvested and assayed at the termination of the experiment, revealing a significant association between Cd and decreased superoxide dismutase (Sod) and catalase activity, decreased total protein and glycogen content, and increased liver and kidney lipid peroxides (LPO) and serum markers of hepatic dysfunction.…”

Possible Regulatory Effects of Application of Alpha Lipoic Acid and Insulin Against Cadmium Exposed Diabetic Rats

“…In studies, it has been shown that Cd increased hyperglycemia and nephrotoxicity in experimentally induced diabetic animals. It has also been shown in these studies that Cd decreases insulin levels and has direct cytotoxic efficacy on the pancreas (5,7). Type 1 diabetic patients are dependent on exogenous insulin (8).…”

“…Cd is regarded greatly toxic and is increasingly bioaccumulated in organism with a biological half-life in people, which is estimated in decades (4). Chronic exposure to Cd results in metal accumulation in tissues and organs, especially in the liver and kidney and causes many histological and metabolic changes, altered gene expression, membrane damage, and apoptosis (5). Cd toxicity is furthermore connected to chancing of redox state and antioxidant system of cells, lipid peroxidation, altered expression of various proteins, and modification in protein structure (6).…”