Effect of a beta 3-adrenergic agonist, BRL35135A, on glucose uptake in rat skeletal muscle in vivo and in vitro.

The effects of the beta 3-agonist, BRL35135A, on glucose uptake in the peripheral tissues of the rat, including skeletal muscle, were studied using the 2-[3H]deoxyglucose method in anaesthetized adult animals. Intravenous infusion of the beta 3-agonist dose-dependently increased the rate constant of glucose uptake in three types of skeletal muscle, brown adipose tissue, white adipose tissue, heart and diaphragm, but not in the brain, spleen or lung. Although infusion of the beta 3-agonist did not change the plasma concentration of glucose appreciably, it caused an increase in the plasma concentration of insulin when given at more than 25 micrograms/kg per h. To ascertain whether the effect of the beta 3-agonist on glucose uptake in skeletal muscle is mediated by insulin, glucose uptake into soleus muscle isolated from young rats was also measured in vitro using different concentrations of the beta 3-agonist. The beta 3-agonist BRL37344 (an active metabolite of BRL35135A) significantly increased glucose transport in a dose-dependent manner, with maximum stimulation at 100 pmol/l. These results demonstrate that glucose uptake in skeletal muscle can be enhanced independently of the action of insulin, probably through the mediation of beta 3-adrenoceptors present in the tissue.