Enhanced metabolism of glucose and glutamine in mesenteric lymph node lymphocytes from spontaneously diabetic BB rats

Abstract

Increased energy substrate metabolism accompanies the functional activation of extrathymic immunocytes in the autoimmune BB diabetic rat, but the specific cells responsible have not been identified. To determine the possible contribution of lymphocytes to the elevated metabolism of glucose and glutamine, mesenteric lymph node cells were selected because they contain few macrophages or natural killer (NK) cells. Results from diabetic (BBd, n = 7) and non-diabetes-prone (BBn, n = 7) rats were compared with those from streptozotocin-induced diabetic (STZ-BBn, n = 6) rats. In BBd cells, all measured metabolites of glutamine (CO2, glutamate, aspartate, and NH3) in the presence of 5 mM glucose were elevated (1.5- to 2.5-fold) compared with BBn. In contrast, the only product of glucose metabolism (in the presence of 2 mM glutamine) that was increased was pyruvate (1.6-fold). All measured products of glucose metabolism were significantly lower in cells from STZ-BBn than from BBn rats. Products from glutamine did not differ. Calculated potential ATP production was greater (p < 0.05) in BBd than in BBn and STZ-BBn cells (86 ± 5 vs. 65 ± 2 and 53 ± 5 nmol∙2 h−1∙10−6 cells, respectively). However, in BBn and STZ-BBn rats, about three quarters of the cells were T (CD5+) cells and one quarter were B (MARK-1+) cells, whereas in BBd three quarters of the cells were MARK-1+. Therefore, to distinguish the role of T- versus B-cells, enriched T-lymphocyte (CD5+) preparations were studied: glutamate (5.3-fold) and NH3 (4.2-fold) production from glutamine and lactate (1.7-fold) production from glucose were greater (p < 0.05) in cells from BBd rats. This establishes that in BBd cells (i) lymphocytes (especially CD4+) contribute to the increased metabolism, (ii) T-lymphocytes are especially active in glutamine metabolism, but because of their reduced numbers, this cannot fully account for the increase in the unfractionated population, and therefore (iii) B-lymphocytes probably also contribute, and (iv) the altered metabolism of these cells is not a result of the diabetic state. These findings are consistent with activation of immunocytes of multiple lineages in this autoimmune syndrome.Key words: glutamine, glucose, lymphocytes, BB rat.