Acute effects of cadmium and selenium on glucose output from rat liver hepatocytes using various gluconeogenic precursors

Abstract

Male Sprague-Dawley rats (250–310 g) fasted for 24 h were injected i.p. with either sodium acetate (C 2H 3NaO 2; 1.23 mg/kg, 15 μmol/kg), cadmium acetate (C 4H 6CdO 4; 0.84 mg/kg, 3.6 μmol/kg), sodium selenite (Na 2SeO 3; 1.6 mg/kg, 9.2 μmol/kg) or cadmium acetate (0.84 mg/kg, 3.6 μmol/kg) and sodium selenite (1.6 mg/kg, 9.2 μmol/kg) simultaneously. Rats were sacrificed 180 min post-treatment and hepatocytes were isolated. An average of 85% cell viability was achieved. Hepatocyte suspension (50 mg cell wt/ml, 1 ml/tube) was incubated for 180 min at 37°/C with 10 mM of one of the following substrates: β- D(−)fructose, glycerol, DL-alanine, L(+)lactic acid or pyruvic acid. Glucose concentration of the supernatant was measured by a colorimetric method. Cadmium decreased glucose output significantly ( P < 0.05), when lactic acid or alanine was used as substrate, but did sigficantly ( P < 0.05) increase the output when pyruvic acid, glycerol or fructose was used. Selenium alone significantly increased ( P < 0.05) hepatic glucose output only when fructose was used as substrate. Selenium and cadmium concurrently administered significantly increased ( P < 0.05) hepatic glucose output when pyruvic acid, glycerol or fructose was used as substrate as compared to sodium acetate (control), cadmium or selenium alone. These findings suggest that cadmium and selenium affect the hepatic gluconeogenic pathway and that their effects depend on the gluconeogenic precursor used.