Acute effect of benfluorex on glucose metabolism.

The antihyperlipidaemic agent benfluorex [1-(3-trifluoromethylphenyl)-2-(2-benzoyl-oxyethyl)-aminopropane] and its metabolite S422 [1-(3-trifluoromethylphenyl)-2-(2-hydroxyethyl)-aminopropane] were examined for an acute (after 1-2 hr) effect on glucose metabolism in normal rats. Enteral administration of benfluorex (25 mg/kg) did not affect basal plasma glucose and insulin concentrations. However, enteral and intravenous glucose tolerance were modestly improved without enhancing the insulin response to glucose. Hepatic gluconeogenesis from lactate was not acutely altered by benfluorex (25 mg/kg) in vivo or by S422 (1 mM) in vitro, but S422 (1 mM) slightly reduced (by 11%) hepatic glycogen mobilization in vitro after 2 hr. S422 (1 mM) increased (by 47%) glucose oxidation by diaphragm muscle in vitro. The effect was additive to that of insulin. Anaerobic glucose metabolism and glycogenesis of diaphragm muscle were not affected by S422. The results suggest that benfluorex can acutely improve glucose tolerance associated with increased glucose oxidation by muscle.

Effects of ephedrine and atenolol on the development of obesity and diabetes in ob/ob mice.

To investigate the involvement of adrenergic mechanisms in the development of obesity, hyperglycaemia and hyperinsulinaemia in Aston ob/ob mice, the sympathomimetic agent ephedrine (12 mg/kg/day) and the predominantly beta 1-adrenergic antagonist atenolol (12 mg/kg/day) were administered alone and in combination to weanling ob/ob mice for 40 days. Excessive weight gain in ob/ob mice was reduced (15-20%) by ephedrine, exacerbated (8-10%) by atenolol, but not significantly altered by a combination of these agents. The effects of ephedrine and atenolol were lost rapidly (within 5 days) when these agents were withdrawn. Ephedrine slightly reduced the hyperphagia in ob/ob mice, and food intake was transiently increased above that of untreated ob/ob mice when this agent was withdrawn. The development of basal hyperglycaemia and hyperinsulinaemia was not significantly altered by any of the treatments studied. None of the treatments significantly altered body weight, food intake, plasma glucose or plasma insulin concentrations in lean (+/+) mice. The results indicate that a defective adrenergic mechanism involving beta 1-adrenergic receptors contributes to the development of obesity in ob/ob mice.

Use of a gamma- or hard beta-emitting radioisotope to assess milk intake in suckling mouse pups.

A radioisotopic method to assess milk intake during suckling in mice is described. The method is based on the transfer of a gamma- or hard beta-emitting radioisotope from the lactating mother to the litter. The radioactivity of individual pups is determined at intervals by whole-body counting. The transfer of 22Na, 32P as orthophosphate, 51Cr as chromate, and 125I as iodide was examined; 125I showed particularly suitable characteristics. The procedure proved to be simple, accurate and reproducible for the comparison of mild consumption between pups within a litter and between litters. The procedure was suitable for studies using a foster mother.