(Hypertension. 2001;38:612.)
© 2001 American Heart Association, Inc.
Cardiovascular Biology |
From the Institute of Internal Medicine and Geriatrics, University of Palermo (M.B., L.J.D.), Italy; and Hypertension Center, New York Presbyterian Hospital/Weill Medical College of Cornell University (O.B., L.M.R.).
Correspondence to Mario Barbagallo, MD, Professor of Medicine, Head of Geriatric Medicine, University of Palermo, Via F. Scaduto 6/c, 90144 Palermo Italy. E-mail mabar{at}unipa.it
Abstract
Abstract Previous studies by our group have identified ionic aspects of insulin resistance in hypertension, in which cellular responses to insulin were influenced by the basal intracellular ionic environmentthe lower the cytosolic free magnesium (Mgi), the less Mgi increased following insulin stimulation. To investigate whether this ionic insulin resistance represents a more general abnormality of cellular responsiveness in hypertension, we studied Mgi responses to nonhormonal signals such as hyperglycemia (15 mmol/L) and used 31P-nuclear magnetic resonance (NMR) spectroscopy to measure Mgi in erythrocytes from normal (NL, n=14) and hypertensive (HTN, n=12) subjects before and 30, 60, 120, and 180 minutes after in vitro glucose incubations. Basal Mgi levels were significantly lower in HTN subjects than in NL subjects (169±10 versus 205±8 µmol·L-1, P<0.01). In NL cells, hyperglycemia significantly lowered Mgi, from 205±8 µmol·L-1 (basal, T=0) to 181±8, 162±6, 152±7, and 175±9 µmol·L-1 (T=30, 60, 120, and 180, respectively; P<0.005 versus T=0 at all times). In HTN cells, maximal Mgi responses to hyperglycemia were blunted, from 169±10 µmol·L-1 (basal, T=0) to 170±11, 179±12, 181±14, and 173±15 µmol·L-1 (T=30, 60, 120, and 180, respectively; P=NS versus T=0 at all times). For all subjects, Mgi responses to hyperglycemia were closely related to basal Mgi levels: the higher the Mgi, the greater the response (n=26, r=0.620, P<0.001). Thus, (1) erythrocytes from hypertensive vis-à-vis normotensive subjects are resistant to the ionic effects of extracellular hyperglycemia on Mgi levels, and (2) cellular ionic responses to glucose depend on the basal Mgi environment. Altogether, these data support a role for altered extracellular glucose levels in regulating cellular magnesium metabolism and also suggest the importance of ionic factors in determining cellular responsiveness to nonhormonal as well as hormonal signals.
Key Words: magnesium hyperglycemia glucose diabetes magnetic resonance spectroscopy
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