Evidence that pioglitazone increases intracellular free magnesium concentration in freshly isolated rat adipocytes

Pioglitazone is one of a new class of oral agents being developed as antidiabetic agents which can increase insulin sensitivity, reduced blood pressure and improve abnormalities in lipid metabolism. The mechanism of action of pioglitazone is not known. Increasing evidence suggests that magnesium can play an important role in regulating glucose homeostasis and vascular tone. To clarify a potential mechanism of pioglitazone action we determined the effects of pioglitazone on intracellular free magnesium concentration in freshly isolated rat adipocytes. Concentrations of pioglitazone as low as 300 nM markedly increased the free magnesium concentration in the adipocytes. Pioglitazone action was selective for magnesium since intracellular free calcium concentration was not altered. These new data suggest that a potentially important mechanism explaining the metabolic and vascular actions of these new anti-diabetic agents is increasing free magnesium concentration in target tissues.