Grden Marzena, Podgorska Marzena, Szutowicz Andrzej, Pawelczyk Tadeusz
Department of Molecular Medicine, Medical University of Gdansk, ul. Debinki 7, paw. 29, 80-211 Gdansk, Poland.
Exp Mol Pathol. 2007 Dec;83(3):392-8. doi: 10.1016/j.yexmp.2007.03.005. Epub 2007 Apr 4.
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.
糖尿病与肝脏的代谢、功能和结构变化相关。已证明腺苷在肝脏中发挥重要的调节作用，其作用与所有四种腺苷受体（ARs）亚型有关。本研究的目的是评估链脲佐菌素诱导的糖尿病对大鼠肝脏中ARs表达水平的影响。所进行的分析（实时PCR、蛋白质印迹法）显示，大鼠肝脏中可检测到A(1)-AR、A(2A)-AR、A(2B)-AR和A(3)-AR的mRNA和蛋白质水平。糖尿病的发展导致A(2A)-AR和A(3)-AR mRNA水平显著增加。这与ARs蛋白含量升高有关。糖尿病肝脏中A(2B)-AR mRNA水平下降约40%，同时肝细胞膜中A(2B)-AR蛋白下降60%。糖尿病不影响肝脏中A(1)-AR的表达水平。给糖尿病大鼠注射胰岛素四天导致ARs表达恢复到正常大鼠肝脏中观察到的水平。ARs基因表达和受体蛋白含量的变化可能与糖尿病肝脏中发生的一些病理变化有关。这可能提示ARs参与了肝脏疾病的发病机制。
