title: Magnesium responsiveness to insulin and insulin-like growth factor I in erythrocytes from normotensive and hypertensive subjects.
abstract: Depletion of intracellular free magnesium (Mg(i)) is a characteristic feature of insulin resistance in essential hypertension, but it is not clear 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). 31P-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 microU/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 micromol/L (P=NS); IGF-I, 164+/-6 to 190+/-11.7 micromol/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 IGF-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.
authors.affiliation: Division of Endocrinology, Metabolism, and Hypertension, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Dominguez
authors.forename: M
authors.initials: M
authors.lastname: Barbagallo
authors.forename: J R
authors.initials: JR
authors.lastname: Sowers
authors.forename: L M
authors.initials: LM
authors.lastname: Resnick
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008274:Magnesium / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012016:Reference Values
chemical_list: D007328:Insulin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D008274:Magnesium