Abstract
Summary
Aim
: Previous studies have reported that β
3
‐adrenergic agonists reduce plasma glucose levels in situations of hyperglycaemia and diabetes in rodents. Nevertheless, the mechanisms still remain unclear. In this context Trecadrine
®
, a novel compound with affinity for β
3
‐adrenergic receptors, has been tested in alloxan‐diabetic rats for its potential use as an anti‐diabetic drug, but also to elucidate the role of muscle/liver glucose utilization in the process.
Methods
and results: Daily oral administration (1 mg/kg) to alloxan‐diabetic Wistar rats (n = 10) for 4 days caused a significant reduction in plasma glucose levels (from 15.0 to 8.3 mmol/l) with no apparent effects on insulin secretion. Furthermore, Trecadrine
®
administration tended to normalize glucose storage (estimated by measuring glucokinase activity) and output (by measuring glucose‐6‐phosphatase activity) in the liver of diabetic animals. On the other hand, Trecadrine
®
administration for 4 days resulted in an increase in GLUT1 gene expression in gastrocnemius muscle as compared to insulin‐dependent glucose transporter GLUT4. Furthermore, a significant stimulation of 2‐deoxy‐
d
‐glucose uptake in extensor digitorum longus muscle and, in a lesser degree, in gastrocnemius, but not in soleus muscle and in white adipose tissue, occurs.
Conclusions
: Trecadrine
®
reduces glucose output from the liver, thus thus contributing to the reduction of plasma glucose levels to achieve the values of control rats. Furthermore, Trecadrine
®
administration stimulates glucose uptake in skeletal muscle, especially in those muscles with predominant glycolytic fast‐twitched fibres, apparently by a direct non‐insulin‐dependent mechanism, involving a relative increase in the content of GLUT1 in the plasma membrane as compared with GLUT4. In conclusion, Trecadrine
®
shows a potent hypoglycaemic effect in the alloxan‐induced model of diabetes in rats by decreasing hepatic glucose output and improving muscle glucose uptake.