Depletion of intracellular free magnesium (Mg(i)) is a characteristic feature of insulin resistance in essential hypertension, but it is not cleat to what extent low Mg(i) levels contribute to insulin resistance, result from it, or both. As insulin-like growth factor I(IGF-I) may improve insulin resistance, we investigated whether this peptide could similarly improve Mg(i) responsiveness to insulin in hypertension, and whether this effect was related to any direct IGF-I effect on Mg(i). (31)P-Nuclear magnetic resonance spectroscopy was used to measure Mg(i) in erythrocytes from 13 fasting normotensive and 10 essential hypertensive subjects before and 30, 60, and 120 min after incubation with a physiologically maximal dose of insulin (200 mu U/mL) and with different doses of recombinant human IGF-I (0.1-100 nmol/L). In normotensive subjects, IGF-I elevated Mg(i) (P < 0.05) in a dose- and time-dependent fashion, as did insulin (P < 0.05). However, in hypertensive subjects, maximal Mg(i) responses to insulin, but not to IGF-I, were blunted [insulin, 163 +/- 11 to 177 +/- 10 mu mol/L (P = NS) IGF-I, 164 +/- 6 to 190 +/- 11.7 mu mol/L (P < 0.05)]. Furthermore, for insulin, but not for IGF-I, cellular Mg(i) responsiveness was closely and directly related to basal Mg(i) levels (insulin: r = 0.72; P < 0.01; IGF-I: r = 0.18; P = NS). Lastly, blunted Mg(i) responses to insulin could be reversed by preincubation of hypertensive cells with EGF-I. We conclude that 1) both IGF-I and insulin stimulate erythrocyte Mg(i) levels; 2) cellular Mg(i) responses to insulin, but not to IGF-I, depend on basal Mg(i) levels, i.e, the higher the Mg(i) the greater the sensitivity to insulin; and 3) IGF-I potentiates insulin-induced stimulation of Mg(i) at doses that themselves do not raise Mg(i). These effects of IGF-I may underlie at least in part its ability to improve insulin sensitivity clinically. Together, these data support a role for IGF-I in cellular magnesium metabolism and emphasize the importance of magnesium as a determinant of insulin action.
Magnesium responsiveness to insulin and insulin-like growth factor I in erythrocytes from normotensive and hypertensive subjects
Dominguez L.J.;
1998-01-01
Abstract
Depletion of intracellular free magnesium (Mg(i)) is a characteristic feature of insulin resistance in essential hypertension, but it is not cleat to what extent low Mg(i) levels contribute to insulin resistance, result from it, or both. As insulin-like growth factor I(IGF-I) may improve insulin resistance, we investigated whether this peptide could similarly improve Mg(i) responsiveness to insulin in hypertension, and whether this effect was related to any direct IGF-I effect on Mg(i). (31)P-Nuclear magnetic resonance spectroscopy was used to measure Mg(i) in erythrocytes from 13 fasting normotensive and 10 essential hypertensive subjects before and 30, 60, and 120 min after incubation with a physiologically maximal dose of insulin (200 mu U/mL) and with different doses of recombinant human IGF-I (0.1-100 nmol/L). In normotensive subjects, IGF-I elevated Mg(i) (P < 0.05) in a dose- and time-dependent fashion, as did insulin (P < 0.05). However, in hypertensive subjects, maximal Mg(i) responses to insulin, but not to IGF-I, were blunted [insulin, 163 +/- 11 to 177 +/- 10 mu mol/L (P = NS) IGF-I, 164 +/- 6 to 190 +/- 11.7 mu mol/L (P < 0.05)]. Furthermore, for insulin, but not for IGF-I, cellular Mg(i) responsiveness was closely and directly related to basal Mg(i) levels (insulin: r = 0.72; P < 0.01; IGF-I: r = 0.18; P = NS). Lastly, blunted Mg(i) responses to insulin could be reversed by preincubation of hypertensive cells with EGF-I. We conclude that 1) both IGF-I and insulin stimulate erythrocyte Mg(i) levels; 2) cellular Mg(i) responses to insulin, but not to IGF-I, depend on basal Mg(i) levels, i.e, the higher the Mg(i) the greater the sensitivity to insulin; and 3) IGF-I potentiates insulin-induced stimulation of Mg(i) at doses that themselves do not raise Mg(i). These effects of IGF-I may underlie at least in part its ability to improve insulin sensitivity clinically. Together, these data support a role for IGF-I in cellular magnesium metabolism and emphasize the importance of magnesium as a determinant of insulin action.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
