Ro-168714

A beta-adrenergic agonist specific for brown adipose tissue, Ro 16-8714, was administered to control and obese insulin-resistant fa/fa rats and glucose utilisation measured in brown adipose tissue using the euglycaemic hyperinsulinaemic clamp combined with the injection of 2-deoxyglucose. Treatment with the beta-agonist increased basal and insulin-stimulated glucose utilization in both groups, resulting in an increased effect of the hormone in treated animals. This effect is specific for brown adipose tissue and is not found in other insulin-sensitive tissue. The total number of insulin-responsive glucose transporters (GLUT4) measured in crude membrane preparations was similar in the two groups when expressed per total tissue. They were, however, decreased in the fa/fa group when expressed per milligram of tissue. Acute treatment with the beta-adrenergic agonist increased the total number of GLUT4 in both groups. The agonist also increased the amount of mRNA coding for GLUT4 suggesting an effect on the transcription and/or on the stability of GLUT4 mRNA.

Streptozotocin (STZ)-induced diabetic rats are glycosuric, hyperglycemic, hyperketonemic, overproduce glucose, and have a decreased glucose utilization in oxidative muscles. Treatment with a beta-agonist, Ro 16-8714, decreases the glycosuria, hyperglycemia, hyperketonemia, and hepatic glucose production. Tissue glucose utilization was unchanged, except in oxidative muscles, where it was increased.