Barbagallo M, Dominguez L J, Bardicef O, Resnick L M
Institute of Internal Medicine and Geriatrics, University of Palermo, Italy.
Hypertension. 2001 Sep;38(3 Pt 2):612-5. doi: 10.1161/hy09t1.095764.
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 environment-the lower the cytosolic free magnesium (Mg(i)), the less Mg(i) increased following insulin stimulation. To investigate whether this ionic insulin resistance represents a more general abnormality of cellular responsiveness in hypertension, we studied Mg(i) responses to nonhormonal signals such as hyperglycemia (15 mmol/L) and used (31)P-nuclear magnetic resonance (NMR) spectroscopy to measure Mg(i) 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 Mg(i) levels were significantly lower in HTN subjects than in NL subjects (169+/-10 versus 205+/-8 micromol.L(-1), P<0.01). In NL cells, hyperglycemia significantly lowered Mg(i), from 205+/-8 micromol.L(-1) (basal, T=0) to 181+/-8, 162+/-6, 152+/-7, and 175+/-9 micromol.L(-1) (T=30, 60, 120, and 180, respectively; P<0.005 versus T=0 at all times). In HTN cells, maximal Mg(i) responses to hyperglycemia were blunted, from 169+/-10 micromol.L(-1) (basal, T=0) to 170+/-11, 179+/-12, 181+/-14, and 173+/-15 micromol.L(-1) (T=30, 60, 120, and 180, respectively; P=NS versus T=0 at all times). For all subjects, Mg(i) responses to hyperglycemia were closely related to basal Mg(i) levels: the higher the Mg(i), 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 Mg(i) levels, and (2) cellular ionic responses to glucose depend on the basal Mg(i) 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.
我们团队之前的研究已经确定了高血压中胰岛素抵抗的离子方面，其中细胞对胰岛素的反应受基础细胞内离子环境的影响——胞质游离镁（Mg(i)）越低，胰岛素刺激后Mg(i)升高越少。为了研究这种离子胰岛素抵抗是否代表高血压中细胞反应性更普遍的异常，我们研究了Mg(i)对非激素信号如高血糖（15 mmol/L）的反应，并使用(31)P-核磁共振（NMR）光谱法测量正常（NL，n = 14）和高血压（HTN，n = 12）受试者体外葡萄糖孵育前以及孵育30、60、120和180分钟后红细胞中的Mg(i)。HTN受试者的基础Mg(i)水平显著低于NL受试者（169±10对205±8 μmol·L(-1)，P<0.01）。在NL细胞中，高血糖显著降低了Mg(i)，从205±8 μmol·L(-1)（基础，T = 0）降至181±8、162±6、152±7和175±9 μmol·L(-1)（分别为T = 30、60、120和180；所有时间点与T = 0相比P<0.005）。在HTN细胞中，对高血糖的最大Mg(i)反应减弱，从169±10 μmol·L(-1)（基础，T = 0）降至170±11、179±12、181±14和173±15 μmol·L(-1)（分别为T = 30、60、120和180；所有时间点与T = 0相比P = 无显著性差异）。对于所有受试者，Mg(i)对高血糖的反应与基础Mg(i)水平密切相关：Mg(i)越高，反应越大（n = 26，r = 0.620，P<0.001）。因此，（1）高血压患者相对于正常血压患者的红细胞对细胞外高血糖对Mg(i)水平的离子效应具有抗性，（2）细胞对葡萄糖的离子反应取决于基础Mg(i)环境。总之，这些数据支持细胞外葡萄糖水平改变在调节细胞镁代谢中的作用，并也表明离子因素在决定细胞对非激素以及激素信号的反应性方面的重要性。
