Parallel Stimulation of Glucose and Mg 2+ Accumulation by Insulin in Rat Hearts and Cardiac Ventricular Myocytes

Abstract

—The stimulation of β-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 β-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 β-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 μmol/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 [³H]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 μmol/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.