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(Hypertension. 2001;38:701.)
© 2001 American Heart Association, Inc.

Obesity- and Diabetes-Related Hypertension

Insulin-Mimetic Action of Vanadate

Role of Intracellular Magnesium

Mario Barbagallo; Ligia J. Dominguez; Lawrence M. Resnick

Institute of Internal Medicine and Geriatrics, University of Palermo (M.B., L.J.D.), Italy; and Hypertension Center, Cornell University Medical School (L.M.R.), New York, NY.

Correspondence to: Mario Barbagallo, MD, Professor of Medicine, Head of Geriatric Medicine, University of Palermo, Via F. Scaduto 6/c, Palermo, Italy. E-mail: mabar{at}unipa.it

Abstract

Abstract—— The insulin-mimetic effect of vanadate is well established, and vanadate has been shown to improve insulin sensitivity in diabetic rats and humans. Although the exact mechanism(s) remain undefined, we have previously demonstrated a direct relation of intracellular free magnesium (Mg_i) levels to glucose disposal, to insulinemic responses following glucose loading, and to insulin-induced ionic effects. To investigate whether the insulin-mimetic effects of vanadate could similarly be mediated by Mg_i, we utilized ³¹P-nuclear magnetic resonance spectroscopy to measure Mg_i in erythrocytes from normal (NL, n=10) and hypertensive (HTN, n=12) subjects, before and after incubation with insulin and with different doses of sodium vanadate. In NL, vanadate elevated Mg_i levels, with maximum efficacy at 50 7mgr;mol/L (186±6 to 222±6 7mgr;mol/L, P>0.01), as did physiologically maximal doses of insulin, 200 7mgr;U/mL (185±6 to 222±8 7mgr;mol/L, P<0.01). In HTN, only vanadate, but not insulin, increased Mg_i (insulin: 173±7 to 180±9 7mgr;mol/L, P=NS; vanadate: 170±7 to 208±10 7mgr;mol/L, P<0.01). Mg_i responses to insulin (r=0.637, P<0.001), but not to vanadate (r=0.15, P=NS), were closely and directly related to basal Mg_i levels. We conclude that (1) both vanadate and insulin stimulate erythrocyte Mg_i levels; (2) cellular Mg_i responses to insulin, but not to vanadate, depend on basal Mg_i content—the lower the basal Mg_i, the less the Mg_i response to insulin. As such, (3) Mg_i responses to vanadate were equivalent among HTN and NL, whereas HTN cells exhibited blunted Mg_i responses to insulin, and (4) the ability of vanadate to improve insulin sensitivity clinically may be mediated, at least in part, by its ability to increase Mg_i levels, which in turn, helps to determine cellular insulin action.

Key Words: magnesium • vanadate • insulin • nuclear magnetic resonance spectroscopy

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