Parallel stimulation of glucose and Mg2+ accumulation by insulin in rat hearts and cardiac ventricular myocytes

The stimulation of beta-adrenoceptors in cardiac cells results in a rapid loss of cellular Mg2+. Because insulin physiologically counteracts several of the cellular effects mediated by the activation of beta-adrenoceptors and the elevation of cytosolic cAMP levels, we investigated whether insulin administration could prevent Mg2+ mobilization from rat hearts and ventricular myocytes. Rat hearts were perfused in a retrograde Langendorff system, and the changes in extracellular Mg2+ were measured by atomic absorbance spectrophotometry. Pretreatment of the hearts with 6 nmol/L insulin completely prevented the Mg2+ extrusion induced by the beta-adrenergic agonist isoproterenol. Furthermore, the administration of insulin per se induced an accumulation of Mg2+ by the heart. This accumulation was small but detectable in the presence of 25 to 35 mu mol/L [Mg2+](o) and increased in proportion to [Mg2+](o). Insulin-mediated Mg2+ accumulation was not observed in hearts perfused with a medium devoid of glucose or with a medium containing the inhibitors of glucose transport, cytochalasin B and phloretin. Insulin-stimulated [H-3]2-deoxyglucose accumulation was measured in collagenase-dispersed cardiac ventricular myocytes in the presence of varying levels of [Mg2+](o). Glucose transport was not observed below 25 mu mol/L [Mg2+](o), and it also increased in proportion to [Mg2+](o). Taken together, these results indicate the presence of a major uptake of Mg2+ into cardiac cells that is stimulated by insulin and may require the insulin-induced operation of a glucose transporter. Hence, extracellular and/or intracellular Mg2+ may modulate glucose transport and/or utilization.