Effect of a beta(3)-adrenergic agonist on liver glucokinase gene expression in alloxan-diabetic rats

beta(3)-adrenergic agonists have been shown to elicit powerful hypoglycemic effects when administered to different animal models of diabetes. However, the intimate mechanism involved in this process remains unclear. In this c ontext, treatment of alloxan-induced diabetic rats with the beta(3)-adrener gic agonist Trecadrine (1 mg.kg(-1).day(-1), s.c.) for four days, normalize d glycemia with no changes in plas ma insulin levels. Liver glucokinase, a key enzyme in the regulation of glucose storage in hepatocytes, whose gene expression is significantly decreased in alloxan-diabetic rodents, showed a recovery in its mRNA levels after Trecadrine administration. These data su ggest that beta(3)-adrenergic agonists enhance glucose storage in liver, pr obably through a non-insulin dependent mechanism of action.