Increase in adenosine A1 receptor gene expression in the liver of streptozotocin‐induced diabetic rats

Abstract

The obtained results suggest that an increase in plasma glucose is responsible for the higher gene expression of A1-AR in the liver of STZ-diabetic rats.

Exercise partially reverses the inhibitory effect of caffeine on liver gluconeogenesis in type 1 diabetic rats with hypoglycemia

“…It is possible that caffeine efficiently blocked the liver adenosine receptors (7,44), making way to an enhancement of the inhibitory effect of insulin on the liver glucose production. This suggestion is consistent with the inhibition of A3-subtype receptors (8,29) and with the results of the in situ liver perfusion for the T1DM+I+C group (Fig. 3).…”

“…In the liver, the adenosine receptors can have many roles concerning glucose metabolism regulation, lipolysis, and inflammation (23,37,48). An increase in the expression of these receptors in the liver in adverse conditions like diabetes could link their activities with the pathogenesis of liver complications in T1DM (7,15,21,29). In addition, situations that increase the levels of ATP hydrolysis, such as exercise and T1DM, are accompanied by increased levels of adenosine (10,35).…”

Novel Mitogenic Effect of Adenosine on Coronary Artery Smooth Muscle Cells

“…Although it is too early to conclude that adenosine is involved in the etiology of coronary artery diseases, several aspects of consideration pertaining to adenosine and the A 1 R point to that potential: (1) the A 1 R is upregulated in diabetes, 33 hypertension, 34 and by oxidative stress, 35 all of which contribute to the development of coronary artery disease; (2) the A 1 R has higher affinity for adenosine than A 2 R, and the desensitization of A 1 R is much slower than A 2 R (t 1/2 : Ϸ10 hours versus Ϸ20 minutes), 36 both properties of which could imply a role for A 1 R in chronic effects on CASMC proliferation; and (3) adenosine is directly released from endothelial cells, stressed myocardial cells, and can also accumulate after catabolism of ATP/ADP released from activated platelets and inflammatory cells surrounding CASMCs after arterial injury. 1 From these points of view, together with the fact that VSMC proliferation is involved in the development of hypertension and atherosclerosis as well as restenosis after angioplasty and bypass surgery, 7,8,32 it is conceivable that identification of a novel mitogenic effect of adenosine and defining its receptor mechanism on CASMC will not only change the paradigm of our current view on the role of adenosine in the coronary circulation and disease, but also imply potential clinical applications via pharmacological intervention such as A 1 R antagonism for limiting the abnormal growth of CASMCs under the aforementioned diseases.…”

“…Therefore, although this compound has been used as a highly selective A 2A R antagonist, caution must be taken when used in pig tissues/cells to differentiate the A 1 R versus A 2A R. The fact that our results differ from results of prior work in VSMCs of other sites exemplifies the prediction made by Ross 32 that VSMCs of different embryonic origins could respond differently to stimuli that generate atherosclerotic lesions in an artery segment-dependent manner. Although it is too early to conclude that adenosine is involved in the etiology of coronary artery diseases, several aspects of consideration pertaining to adenosine and the A 1 R point to that potential: (1) the A 1 R is upregulated in diabetes, 33 hypertension, 34 and by oxidative stress, 35 all of which contribute to the development of coronary artery disease; (2) the A 1 R has higher affinity for adenosine than A 2 R, and the desensitization of A 1 R is much slower than A 2 R (t 1/2 : Ϸ10 hours versus Ϸ20 minutes), 36 both properties of which could imply a role for A 1 R in chronic effects on CASMC proliferation; and (3) adenosine is directly released from endothelial Figure 7. Effects of PTX and PD81723 on the DNA synthesis of CASMCs.…”

Purinergic signalling in the liver in health and disease

“…ATP has been shown to increase insulin secretion in normal and alloxan diabetic rats and influence liver function [235]. An increase in adenosine A 1 receptor expression was claimed in the liver of streptozotocin (STZ)-induced diabetic rats [168]. A later paper showed a significant increase in A 2A and A 3 receptor mRNA levels, whilst A 2B receptor mRNA decreased and A 1 receptors were unchanged; administration of insulin for 4 days to the STZ rats led to return to control levels of P1 receptor expression [106].…”