Streptozotocin-induced diabetes impairs Mg2+ homeostasis and uptake in rat liver cells.
Male Sprague-Dawley rats rendered diabetic by streptozotocin injection presented 10 and 20% decreases in total hepatic Mg2+ content at 4 and 8 wk, respectively, following diabetes onset. This decrease was associated with a parallel decrease in K+ and ATP content and an increase in Na+ level. In diabetic liver cells, the Mg2+ extrusion elicited by alpha1-adrenoceptor stimulation was markedly reduced compared with nondiabetic livers, whereas that induced by beta-adrenoceptor stimulation was unaffected. In addition, diabetic hepatocytes did not accumulate Mg2+ following stimulation of protein kinase C pathway by vasopressin, diacylglycerol analogs, or phorbol 12-myristate 13-acetate derivates despite the reduced basal content in cellular Mg2+. Experiments performed in purified plasma membrane from diabetic livers located the defect at the level of the bidirectional Na+/Mg2+ exchanger operating in the basolateral domain of the hepatocyte cell membrane, which could extrude but not accumulate Mg2+ in exchange for Na+. The impairment of Mg2+ uptake mechanism, in addition to the decrease in cellular ATP level, can contribute to explaining the decrease in liver Mg2+ content observed under diabetic conditions.
Fagan
Theresa E
TE
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
Cefaratti
Christie
C
Romani
Andrea
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D017920:Antiporters / Q000378:metabolism; D001692:Biological Transport; D002412:Cations / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006706:Homeostasis; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000316:Adrenergic alpha-Agonists; D017920:Antiporters; D002412:Cations; C046250:sodium-magnesium antiporter; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D008274:Magnesium