Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 309, Issue 8, Pages G635-G647Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00160.2015
Keywords
copper absorption; iron deficiency; iron-deficiency anemia; iron-refractive iron-deficiency anemia; manganese absorption; SLC11A2; zinc metabolism
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Funding
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01-DK-080047]
- Univ. of Cincinnati Medical Student Summer Research Program
- NIDDK Short-Term Medical Student Training Grant [DK-060444]
- NIDDK [P30-DK-078392, R01-DK-074192]
- Swedish Research Council (SRC) [524-2014-1]
- U.S. Department of Energy (DoE), Nuclear Physics Isotope Program
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Divalent metal-ion transporter-1 (DMT1) is a widely expressed iron-preferring membrane-transport protein that serves a critical role in erythroid iron utilization. We have investigated its role in intestinal metal absorption by studying a mouse model lacking intestinal DMT1 (i.e., DMT1(int/int)). DMT1(int/int) mice exhibited a profound hypochromic-microcytic anemia, splenomegaly, and cardiomegaly. That the anemia was due to iron deficiency was demonstrated by the following observations in DMT1(int/int) mice: 1) blood iron and tissue nonheme-iron stores were depleted; 2) mRNA expression of liver hepcidin (Hamp1) was depressed; and 3) intraperitoneal iron injection corrected the anemia, and reversed the changes in blood iron, nonheme-iron stores, and hepcidin expression levels. We observed decreased total iron content in multiple tissues from DMT1(int/int) mice compared with DMT1(+/+) mice but no meaningful change in copper, manganese, or zinc. DMT1(int/int) mice absorbed Cu-64 and Mn-54 from an intragastric dose to the same extent as did DMT1(+/+) mice but the absorption of Fe-59 was virtually abolished in DMT1(int/int) mice. This study reveals a critical function for DMT1 in intestinal nonheme-iron absorption for normal growth and development. Further, this work demonstrates that intestinal DMT1 is not required for the intestinal transport of copper, manganese, or zinc.
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