Insulin and glucose mediate opposite intracellular ionized magnesium variations in human lymphocytes.
Insulin is capable of increasing intracellular magnesium, although very little is known about the effect of insulin on the biologically active fraction of magnesium, i.e. the ionized quota (Mg(i)(2+)), its interactions with glucose, and the cellular mechanisms involved in these processes. We studied the interactions of the effects of insulin and glucose on intracellular ionized magnesium in human lymphocytes. Mg(i)(2+) was measured using a fluorimetric method and the Mg(2+)-sensitive dye, furaptra. We found that insulin significantly increases the Mg(i)(2+)(without insulin 227 +/- 14 microM, with 10 microU/ml, insulin 301 +/- 30 microM, P<0.0001, n = 12) in a dose-dependent manner in all three glucose concentrations tested (5, 7 and 15 mmol/l). The half-maximal effect of insulin was approximately 0.8 microU/ml. Glucose and insulin showed opposite effects in their ability to modify Mg(i)(2+) in lymphocytes. Inhibitors of the membrane Na(+)- Mg(2+) transport system and of phosphatidylinositol (PI) 3-kinase abolish the insulin-mediated increase of Mg(i)(2+), thus suggesting that insulin is capable of increasing Mg(i)(2+) by modulating the activity of this transport system, possibly through the mediation of PI 3-kinase activation. Taking into account the relationship between insulin and glucose plasma levels and their opposing effects on Mg(i)(2+), this mechanism may represent the two limbs of a biphasic regulatory system of Mg(i)(2+) in both physiological and pathological conditions.
Delva
P
P
Department of Biomedical and Surgical Sciences, Section of Medicina Interna C, University of Verona, Policlinico GB Rossi, Piazzale LA Scuro, 37134 Verona, Italy. pietro.delva@univr.it
Degan
M
M
Trettene
M
M
Lechi
A
A
D000255:Adenosine Triphosphate / Q000032:analysis; D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry; D005470:Fluorometry; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D042541:Intracellular Space / Q000737:chemistry; D007477:Ions; D008214:Lymphocytes / Q000737:chemistry / Q000378:metabolism*; D008274:Magnesium / Q000032:analysis / Q000378:metabolism*; D015388:Organelles / Q000737:chemistry
D007328:Insulin; D007477:Ions; D000255:Adenosine Triphosphate; D008274:Magnesium; D005947:Glucose; D002118:Calcium