Gastrointestinal function, divalent metal transporter-1 expression and intestinal iron absorption

Iron absorption involves two carriers, one involved in the uptake of iron a cross the microvillus membrane of the enterocyte and the other in its trans fer to the plasma at the basolateral surface. The uptake phase is thought C o involve divalent metal transporter-1 (DMT1) which may move from the cytop lasm to the microvillus membrane under conditions of iron deficiency. To ex amine this possibility we used fasted animals previously fed an iron-defici ent diet and then gavaged with iron. We measured the processes of iron abso rption using in vivo gut sacs and correlated the changes observed with the intensity of DMT1 staining and gene expression in the duodenum. Fasting res ulted in increased iron absorption, whereas gavage with iron decreased abso rption. These changes were due to alterations in the uptake phase of absorp tion but not the transfer phase. There was also a highly significant correl ation between the reduction in iron absorption, microvillus DMT1 staining a nd messenger ribonucleic acid (mRNA) expression. The loss of DMT1 from the microvillus membrane was not associated with an increase in cytoplasmic sta ining, suggesting that its loss was due to destruction of the carrier prote in. It is concluded that DMT1 functional activity is determined by de novo synthesis and that the latter is regulated post-transcriptionally by entero cyte iron levels.