Diabetes causes marked changes in lymphocyte metabolism.
An enhanced susceptibility to infections is well known to occur in a poorly controlled diabetic state. Since glucose and glutamine are essential for lymphocyte function, we investigated whether their metabolism is changed in lymphocytes obtained from mesenteric lymph nodes of alloxan-induced diabetic rats (40 mg/kg body weight). The activities of hexokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase (G6PDH), citrate synthase and phosphate-dependent glutaminase were determined. Decarboxylation of metabolites [U-14C]-, [1-14C]- and [6-14C]-glucose, [1-14C]- and [2-14C]-pyruvic acid, [U-14C]-palmitic acid and [U-14C]-glutamine was evaluated in incubated lymphocytes isolated from mesenteric lymph nodes. The measurements were carried out in cells following three experimental protocols: (1) lymphocytes freshly obtained from control and alloxan-induced diabetic rats, (2) lymphocytes from insulin-treated (2 U/rat per day) diabetic rats and (3) lymphocytes obtained from control and diabetic rats and cultured in the presence of insulin (1 mU/ml) for 6 h. The activities of hexokinase, G6PDH and citrate synthase were decreased by the diabetic state, whereas that of phosphofructokinase was raised. Decarboxylation of [U-14C]- and [6-14C]-glucose, [1-14C]- and [2-14C]-pyruvate and [U-14C]-glutamine were also decreased in lymphocytes from diabetic rats, whereas [U-14C]-palmitic acid decarboxylation was increased. Insulin administration in vivo or added to the culture medium reversed the changes observed in freshly obtained lymphocytes. Alloxan-induced diabetes did change lymphocyte metabolism and this may be an important mechanism leading to impairment of lymphocyte function.
Otton
R
R
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524, 05508-900 Butantan, São Paulo, Brazil. rose@fisio.icb.usp.br
Mendonça
J R
JR
Curi
R
R
D000818:Animals; D002478:Cells, Cultured; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005972:Glutaminase / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D025221:Phosphofructokinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005954:Glucosephosphate Dehydrogenase; D002950:Citrate (si)-Synthase; D025221:Phosphofructokinases; D006593:Hexokinase; D005972:Glutaminase