Diabetes-induced alterations of adenosine receptors expression level in rat liver

Abstract

Diabetes mellitus is associated with metabolic, functional, and structural changes in the liver. Adenosine has been demonstrated to play an important regulatory role in the liver, and its action has been associated with all four adenosine receptors (ARs) subtypes. The goal of this study was to evaluate the impact of streptozotocin-induced diabetes on expression level of ARs in rat liver. Performed analyses (real-time PCR, Western blots) revealed detectable levels of mRNA and protein of A(1)-AR, A(2A)-AR, A(2B)-AR, and A(3)-AR in the rat liver. Development of diabetes resulted in a significant increase of A(2A)-AR and A(3)-AR mRNA levels. This was associated with elevated ARs protein content. The level of A(2B)-AR mRNA in diabetic liver decreased approximately 40% and was accompanied by 60% drop in A(2B)-AR protein in liver membranes. Diabetes did not affect the expression level of A(1)-AR in the liver. Administration of insulin for four days to diabetic rats resulted in returning of the ARs expression to the levels observed in liver of normal rat. The changes in ARs genes expression and receptors protein content could be related to some pathological changes taking place in diabetic liver. This might suggest involvement of ARs in pathogenesis of liver disease.