possible antidiabetic role of selective beta-3 adrenoceptor agonist in animal models of diabetes mellitus

ABSTRACT

Control of blood glucose is a key objective in the management of type I and type II diabetes mellitus [DM] as well. The basis for development of new antidiabetic drug is the proper control of the hyperglycemia and furthermore could manage accompanying [isomers especially dyslipidemia. The aim of this study was to investigate a newly developed Beta-3 adrenergic agonist [BRL 37344] to confirm its effect on blood glucose in two animal models of DM. which induced by streptozotocin [STZ] in a dose of 70 or 40 mg/kg for induction of type I or II D. M, respectively and try to explore for the possible underlying mechanism this effect. Oral administration of BRL 37344 for 4 successive days in either STZ type I or STZ type II diabetic rats produced significant reduction in mean serum glucose level and non-significant change in mean serum insulin level in comparison with non treated STZ diabetic rats. BRL treatment significantly increased glucokinase activity and decreased glucose-6-phosphatase activity in hemogenated hepatic tissues which were isolated from both STZ diabetic rat models. In in-vitro study, BRL. produced non-signiticant changes in insulin secretion from isolated pancreatic tissue of STZ type II diabetic rats, while BRL showed significant increase in glucose uptake by isolated soleus muscle from both STZ diabetic rat models. These results showed that selective stimulation of the [Beta-3 -adrenoceptors in diabetic rats, produced significant antihyperglycemic effect. This effect is not through stimulation of pancreatic insulin secretion but it is through inhibition of hepatic glucose output or enhanced glucose utilization by skeletal muscles