Influence of nalmefene on energy balance and glucose regulation in Zucker rats.

It has been hypothesized that opioid peptides play a role in the development of obesity. The opiate antagonist naltrexone decreases glucose-stimulated insulin release, while the sensitivity of diabetic rats to naloxone-induced satiety is increased. These findings suggest a possible interaction between glucose concentrations and opiate antagonists in the control of food intake. In three experiments the energy balance and glucose regulatory responses of Zucker obese and lean rats to chronic administration of nalmefene, an opiate antagonist, were measured. Nalmefene, when injected subcutaneously or added to feed for 21 days, decreased food intake and weight gain of obese and lean rats. These responses were more pronounced during the first week of treatment and were greater in obese than lean rats. Nalmefene increased glucose concentrations during day 1 and weeks 1, 2 and 3 only when given subcutaneously. Nalmefene given intragestrically attenuated glucose-stimulated increases in insulin release only in obese rats. Thus, chronic nalmefene administration is not likely to be an effective treatment for obesity or diabetes.