Metabolic and Biosynthetic Features of Lymphocytes from Patients with Diabetes Mellitus: Similarities to Lymphocytes in Chronic Lymphocytic Leukaemia

Abstract

S ummary This study assayed glucose utilization via the hexose monophosphate (HMP) shunt and Embden‐Meyerhof pathways in lymphocytes from patients with diabetes mellitus (DM) and chronic lymphocytic leukaemia (CLL) employing the quantitative evolution of 14 CO 2 and production of radioactive glycolytic intermediates from [1‐ 14 C]glucose as respective experimental endpoints. In addition, DNA synthesis, as reflected by [ 14 C]thymidine incorporation by the same cells in tissue culture, was measured. Most diabetic lymphocytes displayed depressed absolute and proportional glucose metabolism through the direct oxidative pathway and also demonstrated decreased incorporation of radioactive thymidine, particularly when the lymphocytes were stimulated by phytohaemagglutinin (PHA). The lymphocytes in chronic lymphocytic leukaemia showed the same abnormalities. Moreover, in all lymphocytes assayed, a correlative, semiquantitative relationship was present between the amount of glucose passing through the HMP pathway, which generates NADPH, and the synthesis of DNA, a process requiring this enzyme for reduction of oxyribonucleotides to deoxyribonucleotides. It is postulated that normal antigenic recognition and satisfactory initiation of the immune responses, as mediated by the lymphocyte, may have a metabolic basis, and that this function appears to be abnormal in most patients with diabetes mellitus in this particular study group.