Pawelczyk T, Sakowicz M, Szczepanska-Konkel M, Angielski S
Department of Molecular Medicine, Medical University of Gdansk, ul. Debinki 7 paw. 29, Gdansk, 80-211, Poland.
Arch Biochem Biophys. 2000 Mar 1;375(1):1-6. doi: 10.1006/abbi.1999.1548.
Adenosine has been implicated as an important endogenous regulator of various tissue functions. In diabetes, the responsiveness of several tissues to adenosine is altered. The aim of this study was to investigate the activities of enzymes metabolizing adenosine in tissues of diabetic rats. The cytosolic activity (V(max)) of adenosine kinase (AK) was decreased by 50% in the kidney and by 40% in the heart and liver of diabetic rats. A decrease in the V(max) of AK in diabetic tissues was not associated with a change in the K(m) for adenosine. Evaluation of AK gene transcript status showed significantly lower levels of AK mRNA in diabetic tissues as compared to normal tissues. In diabetic kidneys, the level of AK gene transcript was lowered by 50% on first day after streptozotocin administration, and these reduced levels were sustained declined during the next 10 days. Smaller changes in AK gene transcript levels were observed in the heart and liver than in the kidney. The cytosolic activities of 5'-nucleotidase, AMP deaminase, and adenosine deaminase were unchanged in kidney, heart, and liver of diabetic rats. These results suggest that the turnover of the AMP-adenosine metabolic cycle might be impaired in diabetic tissues due to the reduced activity of adenosine kinase.
腺苷被认为是各种组织功能的重要内源性调节因子。在糖尿病中，几种组织对腺苷的反应性会发生改变。本研究的目的是调查糖尿病大鼠组织中腺苷代谢酶的活性。糖尿病大鼠肾脏中腺苷激酶（AK）的胞质活性（Vmax）降低了50%，心脏和肝脏中降低了40%。糖尿病组织中AK的Vmax降低与腺苷的米氏常数（Km）变化无关。对AK基因转录状态的评估显示，与正常组织相比，糖尿病组织中AK mRNA水平显著降低。在糖尿病肾脏中，链脲佐菌素给药后第一天AK基因转录水平降低了50%，在接下来的10天里这些降低的水平持续下降。在心脏和肝脏中观察到的AK基因转录水平变化比肾脏中的小。糖尿病大鼠肾脏、心脏和肝脏中5'-核苷酸酶、AMP脱氨酶和腺苷脱氨酶的胞质活性没有变化。这些结果表明，由于腺苷激酶活性降低，糖尿病组织中AMP-腺苷代谢循环的周转可能受损。
