Myasthenia gravis, haemolytic anaemia, and lymphoreticular malignancy.

DISCUSSION Adipose tissue from the adult diabetics tested in this study shows a pronounced reduction in activity of phosphofructokinase. This appears even when the enzyme is maximally activated by sulphate ions and suggests that there is an absolute reduction in level of enzyme protein. Phosphofructokinase is an enzyme which is thought to exert control over glycolysis by activation/inhibition reactions which are mediated by a variety of small metabolites (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, phosphate, and citrate). Our data might indicate that over a long-term the level of the enzyme protein alters too. An unexpected observation was that in human diabetic tissue there was no associated depression in activity of hexokinase, despite the reports (Katzen, 1966; McLean et al., 1967) that this enzyme is reduced in adipose tissue of rats made diabetic by streptozotocin or alloxan. Perhaps hexokinase disappears only in states of absolute insulin deficiency, and our diabetic group would not fall into this category since the majority required no insulin therapy. As regards the functional significance of this alteration in enzyme activity, intact adipose tissue of adult diabetics metabolizes less glucose than tissue from non-diabetics (Field et al., 1961; Kahlenberg and Kalant, 1964). This has been attributed to a defect in membrane transport of glucose into the diabetic cell (Kahlenberg and Kalant, 1964). Our data, however, raise the possibility that an intracellular deficiency of a key glycolytic enzyme, phosphofructokinase, might impair glucose utilization by the whole cell and perhaps contribute to the delayed clearance of blood glucose during a tolerance test.