Lack of insulin impairs Mg2+ 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 beta-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 beta-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.
Reed
Grant
G
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Cefaratti
Christie
C
Berti-Mattera
Liliana N
LN
Romani
Andrea
A
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000378:metabolism; D015398:Signal Transduction; D013311:Streptozocin / Q000494:pharmacology*
D007328:Insulin; D011941:Receptors, Adrenergic; D013311:Streptozocin; D000255:Adenosine Triphosphate; D008274:Magnesium