Effect of a beta3-adrenergic agonist on liver glucokinase gene expression in alloxan-diabetic rats.

Beta-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 context, treatment of alloxan-induced diabetic rats with the beta3-adrenergic agonist Trecadrine (1 mg x kg(-1) x day(-1), s. c.) for four days, normalized glycemia with no changes in plasma 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 suggest that beta3-adrenergic agonists enhance glucose storage in liver, probably through a non-insulin dependent mechanism of action.