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(Hypertension. 1999;34:76-82.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Effects of Glutathione on Red Blood Cell Intracellular Magnesium

Relation to Glucose Metabolism

Mario Barbagallo; Ligia J. Dominguez; Maria Rosaria Tagliamonte; Lawrence M. Resnick; Giuseppe Paolisso

From the Institute of Internal Medicine and Geriatrics, University of Palermo (Italy) (M.B., L.J.D.); Division of Endocrinology, Metabolism and Hypertension, Wayne State University, Detroit, Mich (L.J.D., L.M.R.); and Department of Geriatric Medicine and Metabolic Diseases, II University of Naples (Italy) (M.R.T., G.P.).

Correspondence to Mario Barbagallo, MD, PhD, viale F. Scaduto 6/c, 90144 Palermo, Italy. E-mail mabar{at}unipa.it

Abstract—Recent evidence suggests that the endogenous antioxidant glutathione may play a protective role in cardiovascular disease. To directly investigate the role of glutathione in the regulation of glucose metabolism in hypertension, we studied the acute effects of in vivo infusions of this antioxidant (alone or in combination with insulin) on whole body glucose disposal (WBGD) using euglycemic glucose clamp and the effects on total red blood cell intracellular magnesium (RBC-Mg) in hypertensive (n=20) and normotensive (n=30) subjects. The relationships among WBGD, circulating reduced/oxidized glutathione (GSH/GSSG) levels, and RBC-Mg in both groups were evaluated. The in vitro effects of glutathione (100 µmol/L) on RBC free cytosolic magnesium (Mg_i) were also studied. In vivo infusions of glutathione (15 mg/minx120 minutes) increased RBC-Mg in both normotensives and hypertensives (1.99±0.02 to 2.13±0.03 mmol/L, P<0.01, and 1.69±0.03 to 1.81±0.03 mmol/L, P<0.01, respectively). In vitro GSH but not GSSG increased Mg_i (179±3 to 214±5 µmol/L, P<0.01). In basal conditions, RBC-Mg values were related to GSH/GSSG ratios (r=0.84, P<0.0001), and WBGD was directly, significantly, and independently related to both GSH/GSSG ratios (r=0.79, P<0.0001) and RBC-Mg (r=0.89, P<0.0001). This was also true when hypertensive and control groups were analyzed separately. On multivariate analysis, basal RBC-Mg (t=6.81, P<0.001), GSH/GSSG (t=3.67, P<0.02), and blood pressure (t=2.89, P<0.05) were each independent determinants of WBGD, with RBC-Mg explaining 31% of the variability of WBGD. These data demonstrate a direct action of glutathione both in vivo and in vitro to enhance intracellular magnesium and a clinical linkage between cellular magnesium, GSH/GSSG ratios, and tissue glucose metabolism.

Key Words: glutathione • magnesium • hypertension, essential • glucose • insulin resistance • antioxidants

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