The Diabetic Leukocyte

Abstract

The metabolism of polymorphonuclear leukocytes in diabetes is reviewed. The available evidence points towards glucose being freely permeable to the cell membrane. Varying results have been obtained on the rate of glucose utilization and glycolysis, probably due to the different experimental conditions employed by various investigators. In this respect, the crowding effect, i.e. the decrease in metabolic rate observed by increasing the cell concentration, is of special importance. When, however, normal and diabetic cells are incubated in a bicarbonate buffer at the same low cell concentration to avoid the crowding effect, a comparison shows that the glycolysis of diabetic cells is decreased. Glucose-6-phosphate and fructose-6-phosphate accumulate in diabetes, suggesting a decreased activity of phosphofructokinase (EC 2.7.1.11). The increase in glucose-6- phosphate concentration is probably responsible for a small decrease in glucose utilization and a slight increase in pentose cycle activity as well as for an increase in the relative amount of glycogen synthetized. Insulin in vivo corrects the metabolic alterations, whereas there is no convincing evidence of an effect of insulin in physiological concentrations in vitro. The crowding effect has been proposed to be due to an inhibition of the activity of phosphofructokinase by the drop in pH which is caused by the accumulation of lactic acid during the incubation. The absence of the crowding effect in diabetic leukocytes has motivated the suggestion that the sensitivity of phosphofructokinase to changes in pH is compromised in diabetes. The amount of glycogen and its synthesis is markedly reduced in diabetes. The total activity of glycogen synthetase, as well as the ability for D to I transformation, is decreased in diabetic cells and normalized by insulin in vivo, no discernible effect of insulin in vitro being present. The respiration of diabetic leukocytes is normal. No conclusive information on lipid or protein metabolism in diabetic leukocytes is available. The function of leukocytes in inflammation appears to be hampered, but no definite corollary to the impaired carbohydrate metabolism has been produced.