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 a ntidiabetic agents which can increase insulin sensitivity, reduce bloo d pressure and improve abnormalities in lipid metabolism. The mechanis m of action of pioglitazone is not known. Increasing evidence suggests that magnesium can play an important role in regulating glucose homeo stasis and vascular tone. To clarify a potential mechanism of pioglita zone action we determined the effects of pioglitazone on intracellular free magnesium concentration in freshly isolated rat adipocytes. Conc entrations of pioglitazone as low as 300 nM markedly increased the fre e magnesium concentration in the adipocytes. Pioglitazone action was s elective for magnesium since intracellular free calcium concentration was not altered. These new data suggest that a potentially important m echanism explaining the metabolic and vascular actions of these new an ti-diabetic agents is increasing free magnesium concentration in targe t tissues. (C) 1994 Academic Press, Inc.