title: Response of hepatic carbohydrate and cyclic AMP metabolism to cadmium treatment in rats.
abstract: Daily intraperitoneal injection of cadmium chloride (0.25 or 1 mg/kg) for 21 or 45 days into rats significantly stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1, 6-diphosphatase, and glucose-6-phosphatase, increased the concentrations of glucose and urea in the blood, and decreased the levels of glycogen in the liver. Whereas chronic cadmium treatment failed to alter adenosine-3',5'-monophosphate phosphodiesterase (phosphodiesterase) activity, the endogenous levels of cyclic AMP (cAMP) and the activity of basal- and fluoride-stimulated forms of hepatic adenylate cyclase (AC) were markedly increased in cadmium-injected animals. Treatment with the higher dose (1.0 mg/kg) of cadmium chloride for 45 days produced greater metabolic alterations in hepatic tissue than those seen with the lower dose (0.25 mg/kg) given for a shorter period of time (21 days). Discontinuation of cadmium administration for 14 days in rats previously injected with cadmium chloride (1 mg/kg per day) for 21 days, failed to reverse the observed changes in hepatic cAMP or carbohydrate metabolism. A similar persistence of metabolic alterations was noted in rats treated with cadmium (1 mg/kg per day) for 45 days and subsequently maintained without additional treatment for 28 days. Administration of an acute dose of cadmium chloride (60 mg/kg) decreased hepatic phosphodiesterase activity and glycogen content 1 h after the injection. In addition, acute cadmium exposure increased blood glucose, serum urea, and hepatic cAMP levels, and produced an augmentation of basal- and fluoride-activated AC. However, the activities of various hepatic gluconeogenic enzymes remained unaffected in animals given an acute dose of cadmium chloride (60 mg/kg). Data provide evidence that suggests that the gluconeogenic potential of liver is markedly enhanced following chronic exposure to cadmium and that the cadmium-induced changes in carbohydrate metabolism may be associated with an enhanced synthesis of cAMP. In addition, the present study shows that the cadmium-induced metabolic alterations persist even after the cessation of cadmium treatment for a period of 28 days.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology*; D050260:Carbohydrate Metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D005459:Fluorides / Q000494:pharmacology; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006029:Glycosuria; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008112:Liver Glycogen; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D011507:Proteinuria; D011766:Pyruvate Carboxylase / Q000378:metabolism; D051381:Rats; D013268:Stimulation, Chemical; D013997:Time Factors; D014508:Urea / Q000097:blood
chemical_list: D001786:Blood Glucose; D008112:Liver Glycogen; D002104:Cadmium; D014508:Urea; D000242:Cyclic AMP; D006597:Fructose-Bisphosphatase; D005952:Glucose-6-Phosphatase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D000262:Adenylyl Cyclases; D011766:Pyruvate Carboxylase; D005459:Fluorides