The effects of phenobarbital, atropine, L-alpha-methyldopa, and DL-propranolol on dieldrin-induced hyperglycemia in the adult rat.
The hyperglycemic response of adult male Wistar rats given dieldrin (63 mg/kg, po) and either phenobarbital (40 mg/kg, ip), atropine (4 mg/kg, sc), L-alpha-methyldopa (200 mg/kg, ip), or DL-propranolol (8 mg/kg, sc) was studied. The hyperglycemia was maximal (73% above control values) 2 hr after exposure to dieldrin alone. Phenobarbital reduced the hyperglycemia by 41% and abolished dieldrin-induced convulsions. It also prevented the increases that dieldrin causes in hepatic phosphoenolpyruvate carboxykinase (PEPCK) activity. These results suggest that the dieldrin-induced hyperglycemia is mediated via the CNS. Atropine prevented the hyperglycemia for 2 hr and delayed the attainment of maximal glucose concentrations for another 2 hr. However, additional atropine 4, 8, 12, and 18 hr after the dieldrin had no effect. Atropine also increased (125%) the time to the onset of dieldrin-induced convulsions. It did not alter hepatic PEPCK activity. L-alpha-Methyldopa decreased (24%) the hyperglycemic response in the first 2 hr after dieldrin treatment. It caused similar reductions in blood glucose when given during the peak hyperglycemic response. L-alpha-Methyldopa also reduced (49%) the dieldrin-effected increase in hepatic PEPCK activity. DL-Propranolol did not alter the effects of dieldrin. Thus these data suggest that the dieldrin-induced hyperglycemia is mediated by the CNS, primarily via enhanced cholinergic activity and secondarily by increased alpha-adrenergic activity. It is suggested that the pancreas responds to the cholinergic outflow by increasing the secretion of glucagon while simultaneously responding to the alpha-adrenergic outflow by decreasing insulin secretion.
D000284:Administration, Oral; D000818:Animals; D001285:Atropine / Q000627:therapeutic use*; D001786:Blood Glucose; D002490:Central Nervous System / Q000187:drug effects*; D004026:Dieldrin / Q000633:toxicity*; D004347:Drug Interactions; D005943:Gluconeogenesis / Q000187:drug effects; D007003:Hypoglycemia / Q000139:chemically induced* / Q000517:prevention & control; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008750:Methyldopa / Q000627:therapeutic use*; D010634:Phenobarbital / Q000627:therapeutic use*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D011433:Propranolol / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D008750:Methyldopa; D001285:Atropine; D011433:Propranolol; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D004026:Dieldrin; D010634:Phenobarbital