In vivo effect of insulin on intracellular calcium concentrations: relation to insulin resistance

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.