Effect of ractopamine on insulin sensitivity and response of isolated rat adipocytes

In vitro effects of the phenethanolamine ractopamine on basal and insulin-stimulated lipid metabolism were determined in adipocytes isolated from epididymal fat pads of Sprague-Dawley rats. Ractopamine appeared to be equipotent to the catecholamine isoproterenol in stimulating basal lipolysis and inhibiting basal lipogenesis, producing maximum effects at 10(-6) M. Addition of a half-maximally stimulating dose of ractopamine (5 x 10(-8) M) to the incubation media decreased insulin sensitivity but not insulin responsiveness of the cells, stimulating lipolysis and inhibiting lipogenesis only in the presence of low media insulin concentrations. This effect was totally reversed by 10 microM/propranolol. Maximally effective concentrations of ractopamine (10(-6) M) significantly decreased both the sensitivity and responsiveness of the isolated adipocytes to insulin. Addition of 10 microM propranolol to the incubation media effectively reversed the lipolytic and anti-lipogenic effects of 10(-6) M ractopamine observed at media insulin concentrations greater than 25 microU/ml, whereas it only partially reduced the ractopamine-induced effects observed at lower insulin concentrations. The results demonstrate 1) that ractopamine has concentration-dependent effects on adipose tissue insulin sensitivity and responsiveness and 2) that these effects may be mediated, in part, through beta-adrenergic receptors.