LACTATE PRODUCTION IS THE MAJOR METABOLIC-FATE OF GLUCOSE IN SPLENOCYTES AND IS ALTERED IN SPONTANEOUSLY DIABETIC BB RATS

Enhanced glucose metabolism is necessary to support the activation and proliferation of lymphocytes. To define further quantitatively the metabolic fates of glucose and assess glucose utilization both in normal cells and in an autoimmune disease with abnormal lymphocytes, [U-14C]glucose conversion into 14CO2 and the production of lactate and pyruvate were measured in splenocytes. Cells from non-diabetes-prone (BBn) and spontaneously diabetic (BBd) rats were studied both freshly isolated 'resting' and cultured for 96 h with and without concanavalin A (Con A) stimulation. (1) Lactate was confirmed to be the major end product in both freshly isolated (53% of utilized glucose) and unstimulated cultured (62% of utilized glucose) cells from BBn animals studied at (2-8)x106 cells/ml concentration. The use of concentrations from 10x106 to 300x106 cells/ml resulted in progressively less lactate production per 106 splenocytes. (2) Cells from BBd animals after stimulation with Con A incorporated less [3H]thymidine and produced significantly less lactate (155±14 versus 305±24 nmol/2 h per 106 cells) than did BBn cells (P<0.05). (3) However, more lactate (101±8 versus 78±6 nmol/5 h per 106 cells) was produced by 'resting' cells from BBd animals compared with BBn (P<0.03), and this difference was sustained after 4 days in culture. (4) Significantly greater amounts of pyruvate were produced by BBd than by BBn cells, particularly when stimulated with Con A, suggesting an alteration in the availability of reducing equivalents in BBd cells. (5) These results are consistent with prior metabolic as well as immunological 'activation' of cells in vivo in the BB diabetic animals.