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

Auton Neurosci. 2015 Dec:193:108-16. doi: 10.1016/j.autneu.2015.10.003. Epub 2015 Nov 5.

Abstract

Objective: Unequivocal 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.

Methods: Insulin-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.

Results: Insulin 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.

Discussion: Propranolol-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.

Keywords: EDL; PKA; SHR; Soleus; TNF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Blood Glucose / drug effects
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Glucose Transporter Type 4 / metabolism*
  • Homeostasis / drug effects
  • Homeostasis / physiology
  • Hypoglycemic Agents / pharmacology*
  • Insulin / pharmacology*
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Propranolol / pharmacology*
  • RNA, Messenger / metabolism
  • Rats, Inbred SHR
  • Rats, Wistar
  • Receptors, Adrenergic, beta-2 / metabolism
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists
  • Blood Glucose
  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Insulin
  • RNA, Messenger
  • Receptors, Adrenergic, beta-2
  • Slc2a4 protein, rat
  • Propranolol
  • Cyclic AMP-Dependent Protein Kinases