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.