Intracellular magnesium and insulin resistance: results in Pima Indians and Caucasians.

Intracellular magnesium is a cofactor for numerous enzymes involved in carbohydrate metabolism. Magnesium accumulation is dependent upon insulin action and correlates with insulin-mediated glucose uptake. As Pima Indians are known to be insulin resistant, we investigated whether, in response to insulin infusion, they have lower erythrocyte magnesium accumulation than Caucasians. Insulin-mediated glucose uptake was determined by a euglycemic hyperinsulinemic glucose clamp in 29 obese nondiabetic volunteers: 15 Caucasians (8 males and 7 females) and 14 Pima Indians (8 males and 6 females). Pima Indians were younger than Caucasians (mean +/- SD, 28 +/- 7 vs. 39 +/- 8 yr; P < 0.01), but had similar body mass index and fasting/2-h plasma glucose concentrations. Despite higher steady state plasma insulin levels (692 +/- 260 vs. 540 +/- 70 pmol/L; P < 0.03), Pima Indians had lower insulin-mediated glucose uptake than Caucasians (108 +/- 20 vs. 244 +/- 32 mg/m2.min; P < 0.0001). The mean fasting plasma magnesium concentration was lower in Pima Indians than in Caucasians (0.79 +/- 0.05 vs. 0.85 +/- 0.06 mmol/L; P < 0.01), whereas the mean fasting erythrocyte magnesium concentrations (1.98 +/- 0.10 vs. 2.03 +/- 0.14 mmol/L) were similar in the 2 groups. In response to insulin infusion, erythrocyte magnesium content increased less in Pima Indians than in Caucasians (0.15 +/- 0.07 vs. 0.28 +/- 0.21 mmol/L; P < 0.03). However, this increase was similar in the 2 groups when values were adjusted for insulin-mediated glucose uptake. In conclusion, nondiabetic Pima Indians have a lower erythrocyte magnesium accumulation in response to insulin infusion; this is probably due to their high degree of insulin resistance. The biochemical and physiological consequences of decreased intracellular magnesium uptake are discussed.