Resting and stimulated human polymorphonuclear leucocytes from type-2 diabetic patients: change in purine nucleotide pattern.

Abstract

It is known that polymorphonuclear leucocytes are deeply involved in the inflammatory complications of diabetes mellitus, showing many functional and biochemical abnormalities. Because adenine and guanine metabolites exert an important role in many metabolic aspects of phagocytic cells, we have investigated the pattern of purine metabolites during the respiratory burst of polymorphonuclear leucocytes in order to characterize any difference that may be significantly correlated with the abnormal neutrophil function of diabetic patients. The results obtained show clearly that polymorphonuclear leucocytes from diabetic patients are characterized by an abnormal pattern of purine nucleotides and their metabolites. In particular, the concentration of adenine and guanine triphosphates and the net amount of adenosine triphosphate hydrolysed during neutrophil stimulation by phorbol ester is higher in diabetic than in control cells. Moreover, higher values of adenosine monophosphate, inosine monophosphate and inosine have been found in diabetic cells. The behaviour of guanosine triphosphate is highly interesting. In fact, in addition to the higher concentration found in diabetic polymorphonuclear leucocytes, stimulation by phorbol ester induces a net decrease in guanosine triphosphate whereas control neutrophils show a slight increase. These findings have been associated with the ease with which diabetic neutrophils undergo metabolic activation and sustain an inflammatory response.