Lack of insulin impairs Mg 2+ homeostasis and transport in cardiac cells of streptozotocin‐injected diabetic rats

Serum and tissue Mg 2+ content are markedly decreased in diabetic patients and animals. At the tissue level, Mg 2+ loss progresses over time and affects predominantly heart, liver and skeletal muscles. In the present study, alterations in Mg 2+ homeostasis and transport in diabetic cardiac ventricular myocytes were evaluated. Cardiac tissue and isolated cardiac ventricular myocytes from diabetic animals displayed a decrease in total Mg 2+ content that affected all cellular compartments. This decrease was associated with a marked reduction in cellular protein and ATP content. Diabetic ventricular myocytes were unable to mobilize Mg 2+ following β‐adrenergic receptor stimulation or addition of cell permeant cyclic‐AMP. Sarcolemma vesicles purified from diabetic animals, however, transported Mg 2+ normally as compared to vesicles from non‐diabetic animals. Treatment of diabetic animals with exogenous insulin for 2 weeks restored ATP and protein levels as well as Mg 2+ homeostasis and transport to levels comparable to those observed in non‐diabetic animals. These results suggest that in diabetic cardiac cells Mg 2+ homeostasis and extrusion via β‐adrenergic/cAMP signaling are markedly affected by the concomitant decrease in protein and ATP content. As Mg 2+ regulates numerous cellular enzymes and functions, including protein synthesis, these results provide a new rationale to interpret some aspects of the cardiac dysfunctions observed under diabetic conditions. J. Cell. Biochem. 104: 1034–1053, 2008. © 2008 Wiley‐Liss, Inc.