Beta-adrenergic blockade increases GLUT4 and improves glycemic control in insulin-treated diabetic Wistar rats

- Unequivocal modulation of glycemia by beta-blockade in DM has never been reported.
- Propranolol increased Slc2a4/GLUT4 in muscle, improving glycemic homeostasis in DM.
- Beta-blockade paradoxically increased PKA activity in muscles from diabetic SHR.

ABSTRACTObjectiveUnequivocal modulation of glycemic homeostasis by chronic beta-adrenergic blockade in diabetes has never been demonstrated. This study investigates the participation of beta-adrenergic system in glycemic control and muscle glucose transporter GLUT4 expression in insulin-treated diabetic rats.MethodsInsulin-treated diabetic Wistar (W) or spontaneously hypertensive rats (SHR) were additionally treated with propranolol, and glycemic homeostasis and expression of some target mRNAs and proteins in soleus and extensor digitorum longus (EDL) muscles were analyzed.ResultsInsulin improved glycemic control in both strains. Importantly, in W, propranolol promoted a further improvement in glycemic control, which was accompanied by decreased PKA and Tnf expression, and increased Slc2a4 and GLUT4 in EDL. Those effects were not observed in diabetic-SHR.DiscussionPropranolol-induced decrease in beta-adrenergic activity in skeletal muscles of insulin-treated diabetic Wistar rats increases GLUT4 expression in EDL, improving glycemic control. These outcomes represent a positive effect of nonselective beta-blockade, which might be extended to autonomic neuropathy.

118