Decreased expression of adenosine kinase in streptozotocin-induced diabetes mellitus rats

Adenosine has been implicated as an important endogenous regulator of vario us tissue functions. In diabetes, the responsiveness of several tissues to adenosine is altered. The aim of this study was to investigate the activiti es of enzymes metabolizing adenosine in tissues of diabetic rats. The cytos olic activity (V-max) of adenosine kinase (AR) was decreased by 50% in the kidney and by 40% in the heart and liver of diabetic rats. A decrease in th e V-max of AR in diabetic tissues was not associated with a change in the K -m for adenosine. Evaluation of AK gene transcript status showed significan tly lower levels of AK mRNA in diabetic tissues as compared to normal tissu es. 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 gen e 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. The se results suggest that the turnover of the AMP-adenosine metabolic cycle m ight be impaired in diabetic tissues due to the reduced activity of adenosi ne kinase. (C) 2000 Academic Press.