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A b 3 ‐adrenergic agonist increases muscle GLUT1/GLUT4 ratio, and regulates liver glucose utilization in diabetic rats*
Author(s) -
Milagro F. I.,
GómezAmbrosi J.,
Forga L.,
Martínez J. A.
Publication year - 1999
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1046/j.1463-1326.1999.00019.x
Subject(s) - medicine , endocrinology , glut4 , glucose transporter , glucose uptake , glut1 , insulin , skeletal muscle , diabetes mellitus , adipose tissue , white adipose tissue , glucokinase , extensor digitorum longus muscle , chemistry , biology
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.