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Activation of adenosine A1receptors by drugs to lower plasma glucose in streptozotocin-induced diabetic rats

Authors
Journal
Autonomic Neuroscience
1566-0702
Publisher
Elsevier
Publication Date
Volume
83
Issue
3
Identifiers
DOI: 10.1016/s0165-1838(00)00106-5
Keywords
  • Adenosine A1Receptor
  • N6-Cyclopentyladenosine
  • Dipyridamole
  • Glucose Uptake
  • Glycogen Synthesis
  • Streptozotocin-Induced Diabetic Rat

Abstract

Abstract To examine the role of the adenosine A 1 receptor in glucose regulation in the absence of insulin, the present study investigated the changes of plasma glucose in male streptozotocin-induced diabetic rats (STZ-diabetic rats) using dipyridamole to increase endogenous adenosine and N 6-cyclopentyladenosine (CPA) to activate the adenosine A 1 receptor. Intravenous injections of dipyridamole or CPA induced a dose-dependent decrease of plasma glucose in fasting STZ-diabetic rats. Plasma glucose lowering action of dipyridamole, like that of CPA, was inhibited in a dose-dependent manner by pre-treatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or 8-( p-sulfophenyl)theophylline (8-SPT) at which block the adenosine A 1 receptors. Action of the adenosine A 1 receptors can thus be considered. In isolated skeletal muscle, CPA enhanced the glucose uptake in a concentration-dependent manner. Blockade of this action by DPCPX and 8-SPT again supported the mediation of the adenosine A 1 receptor. Also, CPA produced an increase of glycogen synthesis in isolated soleus muscle. Moreover, CPA decreased plasma triglyceride and cholesterol levels significantly in STZ-diabetic rats. These results suggest that activation of adenosine A 1 receptors can increase glucose utilization in peripheral tissues by increasing tissue uptake and glycogen synthesis to lower plasma glucose in rats lacking insulin.

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