Divalent metal transporter-1 (DMT1) mediates dietary nonheme iron absorption. Belgrade ( b) rats have defective iron metabolism due to a mutation in the DMT1 gene. To examine the role of DMT1 in neonatal iron assimilation, b/b and b/+ pups were cross-fostered to F344 Fischer dams injected with59FeCl3twice weekly during lactation. Tissue distribution of the radioisotope in the pups was determined at weaning ( day 21). The b/b pups had blood59Fe levels significantly lower than b/+ controls but significantly higher59Fe tissue levels in heart, bone marrow, skeletal muscle, kidney, liver, spleen, stomach, and intestines. To study the pharmacokinetics of nonheme iron absorption at the time of weaning,59FeCl3was administered to 21-day-old b/b and b/+ rats by intragastric gavage. Blood59Fe levels measured 5 min to 4 h postgavage were significantly lower in b/b rats, consistent with impaired DMT1 function in intestinal iron absorption. Tissue59Fe levels were also lower in b/b rats postgavage. Combined, these data suggest that DMT1 function is not essential for iron assimilation from milk during early development in the rat.
Increased duodenal iron absorption through up-regulation of divalent metal transporter 1 from enhancement of iron regulatory protein 1 activity in patients with nonalcoholic steatohepatitis