Streptozotocin-induced diabetes impairs Mg2+homeostasis and uptake in rat liver cells

Abstract

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 α1-adrenoceptor stimulation was markedly reduced compared with nondiabetic livers, whereas that induced by β-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.