TY - JOUR
T1 - Erythrocyte glutathione concentration and production during hyperinsulinemia, hyperglycemia, and endotoxemia in healthy humans
AU - van der Crabben, Saskia N.
AU - Stegenga, Michiel E.
AU - Blümer, Regje M. E.
AU - Ackermans, Mariëtte T.
AU - Endert, Erik
AU - Tanck, Michael W. T.
AU - Serlie, Mireille J.
AU - van der Poll, Tom
AU - Sauerwein, Hans P.
N1 - Copyright © 2011 Elsevier Inc. All rights reserved.
PY - 2011/1
Y1 - 2011/1
N2 - In diabetes mellitus and sepsis, low erythrocyte glutathione (GSH) concentrations are found. Whether this is caused by lowered GSH production has not been clarified. To obtain insight in the relationship between erythrocyte GSH concentrations and GSH production, GSH kinetics were measured in healthy male volunteers during 4 different clamps (low-dose or medium-dose insulin [100 or 400 pmol/L] and euglycemia or hyperglycemia [5 or 12 mmol/L]) in a control setting (n = 6; all 4 clamps in the same subject) or after systemic administration of lipopolysaccharide (to mimic sepsis) (4 groups of n = 6; each clamp in a different subject). Hyperinsulinemia decreased erythrocyte GSH concentration (P = .042), but did not affect fractional synthetic rate (FSR) of GSH. Hyperglycemia did not affect erythrocyte GSH concentration, but decreased FSR of GSH (P = .025). Lipopolysaccharide decreased erythrocyte GSH concentration (P < .001), but increased FSR of erythrocyte GSH (P = .035). Depending on the metabolic circumstances, we found either stable GSH concentrations with lower production rates or decreased levels with either no change or an increase in production rate. Based upon these data, it seems inappropriate to infer conclusions about changes in synthesis rate of GSH from changes in its concentration.
AB - In diabetes mellitus and sepsis, low erythrocyte glutathione (GSH) concentrations are found. Whether this is caused by lowered GSH production has not been clarified. To obtain insight in the relationship between erythrocyte GSH concentrations and GSH production, GSH kinetics were measured in healthy male volunteers during 4 different clamps (low-dose or medium-dose insulin [100 or 400 pmol/L] and euglycemia or hyperglycemia [5 or 12 mmol/L]) in a control setting (n = 6; all 4 clamps in the same subject) or after systemic administration of lipopolysaccharide (to mimic sepsis) (4 groups of n = 6; each clamp in a different subject). Hyperinsulinemia decreased erythrocyte GSH concentration (P = .042), but did not affect fractional synthetic rate (FSR) of GSH. Hyperglycemia did not affect erythrocyte GSH concentration, but decreased FSR of GSH (P = .025). Lipopolysaccharide decreased erythrocyte GSH concentration (P < .001), but increased FSR of erythrocyte GSH (P = .035). Depending on the metabolic circumstances, we found either stable GSH concentrations with lower production rates or decreased levels with either no change or an increase in production rate. Based upon these data, it seems inappropriate to infer conclusions about changes in synthesis rate of GSH from changes in its concentration.
KW - Blood Glucose/analysis
KW - Cross-Over Studies
KW - Endotoxemia/metabolism
KW - Erythrocytes/metabolism
KW - Glutathione/biosynthesis
KW - Humans
KW - Hyperglycemia/metabolism
KW - Hyperinsulinism/metabolism
KW - Insulin/blood
KW - Lipopolysaccharides/pharmacology
KW - Male
U2 - https://doi.org/10.1016/j.metabol.2010.08.003
DO - https://doi.org/10.1016/j.metabol.2010.08.003
M3 - Article
C2 - 20850847
SN - 0026-0495
VL - 60
SP - 99
EP - 106
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 1
ER -