Naltrexone reduces weight gain, alters "beta-endorphin", and reduces insulin output from pancreatic islets of genetically obese mice.
Naltrexone, an opiate antagonist, was administered to young obese (ob/ob) and lean mice for five weeks. Animals had continuous access to food and received 10 mg/kg SC twice daily with equivalent volumes of saline given to controls. The effects on body weight, and pituitary and plasma levels of beta-endorphin-like material were measured. Naltrexone-injected obese animals gained weight more slowly over the first three weeks while the weight gain of lean animals was not affected by naltrexone. Plasma levels of beta-endorphin were shown to be significantly higher in untreated ob/ob mice and this difference increased with age (4-20 weeks). With naltrexone treatment, plasma levels in +/? mice rose and exceeded those in ob/ob. Saline treatment appeared to be a stress, and pituitary beta-endorphins rose 4-6 fold in ob/ob compared with +/?. While naltrexone reduced the levels of ob/ob pituitary towards normal, no effect on beta-endorphin levels in pituitary of lean mice was obtained. In vitro studies of effects of the opiate antagonists, naloxone, on insulin secretion by isolated islets provided additional evidence of resistance of lean mice to naloxone relative to ob/ob. (IRI secretion fell only in naloxone treated ob/ob islets). These observations support the contention that this form of genetic obesity is characterized by elevated endogenous opiate levels and an increased sensitivity to opiate antagonists such as naltrexone or naloxone.
D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D004723:Endorphins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009270:Naloxone / Q000031:analogs & derivatives*; D009271:Naltrexone / Q000494:pharmacology*; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology; D010902:Pituitary Gland / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects; D001615:beta-Endorphin
D004723:Endorphins; D007328:Insulin; D011957:Receptors, Opioid; D009270:Naloxone; D009271:Naltrexone; D001615:beta-Endorphin