ADENOSINE TRANSPORT BLOCKER PROTECTS THE PANCREAS FROM WARM ISCHEMIA: A POSSIBLE ROLE IN PANCREATIC TRANSPLANTATION
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Adenine metabolite pool especially ATP concentration is a reliable index of cellular energy state of viable tissues. In this work both adenine metabolite pool of canine pancreas and ATPase activity of isolated mitochondria and microsomes in basal state and during normothermic ischemia were detected. This may give information about its susceptibility to tissue ischemia . It may occur during the time elapsed between its separation and transplantation. Moreover the effect of cytoprotective agent nitrobenzyl thioinosine on above mentioned parameters was determined. The study revealed that pancreas is more vulnerable to the metabolic sequelae of tissue ischemia due to low basal level of ATP and high ATPase activity . Normothermic ischemia depleted ATP, ADP and adenosine contents after 20 minutes . Precursors of free radicals namely inosine level was significantly increased. NBMPR improved the tolerability of isolated pancreas to tissue ischemia. It delayed the ischemic mediated depletion of ATP by inhibiting its of breakdown by mitochondrial and microsomal ATP ases and activation of its salvage through increasing the availability of its precursor (adenosine). Moreover de-novo ATP synthesis may be enhanced by stimulation of glycolysis . This may rationalize the use of the tested drug during islet cell or whole pancreatic transplantation. Its in-vivo use to prolong islet cell survival after transplantation needs detailed study on its effect on carbohydrate metabolism in diabetic patients.