Age-related susceptibility to the insulin-depleting action of 4-diphenylmethylpiperidine in young rats.
Studies were undertaken to investigate age-related changes in the ability of 4-diphenylmethylpiperidine (4-DPMP) to reduce levels of pancreatic insulin in young rats. Oral doses of 4-DPMP (5.0 or 10.0 mg/kg) were given once daily for two days to 9-, 15- and 21-day-old rats. Twenty-four hours after the last dose, pancreatic insulin content, non-fasting serum glucose, and the amount of unchanged 4-DPMP present in the whole body were estimated. 4-DPMP treatment produced a decline in pancreatic insulin and the extent of this action was greater in younger animals. The observed changes in pancreatic insulin were not reflected in altered serum glucose levels, showing this parameter is a relatively poor indicator of pancreatic insulin loss. Younger animals had a larger fraction of the total dose of 4-DPMP in the body at the end of the experimental period when compared to the fraction retained by older rats. The age-related susceptibility of young rats to the diabetogenic action of 4-DPMP may be related to the differences in the rate of elimination of the chemical at different ages.
Chatterjee
A K
AK
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Fischer
L J
LJ
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D005260:Female; D007328:Insulin / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D010880:Piperidines; C056520:4-diphenylmethylpiperidine