Baldi S, Natali A, Buzzigoli G, Galvan A Q, Sironi A M, Ferrannini E
Metabolism Unit, Consiglio Nazionale delle Ricerche (CNR) Institute of Clinical Physiology, Pisa, Italy.
Metabolism. 1996 Nov;45(11):1402-7. doi: 10.1016/s0026-0495(96)90122-5.
Elevated intracellular calcium concentrations ([Ca2+]i) have been described in essential hypertension and other insulin-resistant states. Our aim was to explore the relationship between insulin resistance and abnormal Ca2+ metabolism. In 50 nondiabetic subjects, half of whom had untreated essential hypertension, we simultaneously measured the in vivo effect of insulin on glucose metabolism (by the insulin clamp technique) and on platelet [Ca2+]i (by the Fura-2 method). In each subject, [Ca2+]i measurements (both in Ca(2+)-free medium and, sequentially, following in vitro Ca2+ loading) were obtained in the fasting state and after 2 hours of euglycemic hyperinsulinemia. In the fasting state, no association was found between any measure of [Ca2+]i and gender, age, body mass index (BMI), blood pressure, or insulin sensitivity. In contrast, following in vivo insulin, platelet [Ca2+]i increased significantly (from 23 +/- 1 to 28 +/- 1 nmol/L in Ca(2+)-free medium, P < .01) in the whole group, and an insulin-induced increase in [Ca2+]i was associated with insulin resistance (r = .35, P = .01) but not with hypertension (r = .2, P = .17) and with impaired glucose storage (as determined by indirect calorimetry, r = .39, P = .01) but not with glucose oxidation. Thus, the 12 most insulin-resistant subjects were characterized by a cluster of abnormalities (mild overweight, higher blood pressure and prevalence of hypertension, higher serum triglycerides and insulin response to oral glucose, and reduced glucose storage) that included an insulin-induced increase in [Ca2+]i (9 +/- 2 nmol/L, P < .001 v basal). We conclude that insulin resistance, rather than hypertension, is associated with an abnormal in vivo effect of insulin on platelet [Ca2+]i.
原发性高血压和其他胰岛素抵抗状态下均有细胞内钙浓度（[Ca2+]i）升高的报道。我们的目的是探讨胰岛素抵抗与异常钙代谢之间的关系。在50名非糖尿病受试者中，其中一半患有未经治疗的原发性高血压，我们同时测量了胰岛素对葡萄糖代谢（采用胰岛素钳夹技术）和血小板[Ca2+]i（采用Fura-2法）的体内效应。在每个受试者中，在空腹状态和正常血糖高胰岛素血症2小时后，均在无钙培养基中以及随后体外钙加载后测量[Ca2+]i。在空腹状态下，未发现任何[Ca2+]i测量值与性别、年龄、体重指数（BMI）、血压或胰岛素敏感性之间存在关联。相比之下，在体内给予胰岛素后，全组血小板[Ca2+]i显著升高（在无钙培养基中从23±1升高至28±1 nmol/L，P<.01），胰岛素诱导的[Ca2+]i升高与胰岛素抵抗相关（r=.35，P=.01），但与高血压无关（r=.2，P=.17），与葡萄糖储存受损相关（通过间接量热法测定，r=.39，P=.01），但与葡萄糖氧化无关。因此，12名胰岛素抵抗最严重的受试者具有一系列异常特征（轻度超重、血压较高及高血压患病率较高、血清甘油三酯较高及口服葡萄糖后胰岛素反应较高、葡萄糖储存减少），其中包括胰岛素诱导的[Ca2+]i升高（9±2 nmol/L，与基础值相比P<.001）。我们得出结论，与高血压相比，胰岛素抵抗与胰岛素对血小板[Ca2+]i的体内异常效应相关。
