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Internalization and Decrease of Duodenal DMT1 Involved in Transient Suppression of Iron Uptake in Short-Acting
Anna Arita1,2, Ichiro Kita3, Shoko Shinoda3
1Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Hachioji, Tokyo, Japan. a-arita@tmu.ac.jp.
Abstract:
Mucosal block (MB) is induced by the oral administration of excess iron (10 mg) and suppresses intestinal iron absorption for 3-72 h. The inhibition of iron absorption is accompanied by the downregulation of molecules associated with intestinal iron absorption. Recently, we found that a smaller amount of iron (1 mg) also induced a transient suppression of iron uptake without affecting gene expression levels (short-acting mucosal block, SAMB), which is specific to iron-deficient rats. In this study, we investigated how the nonheme iron transporters divalent metal transporter 1 (DMT1) and ferroportin (FPN) are involved in the transient suppression of iron uptake in SAMB. To induce SAMB, a test solution containing 1 mg iron was infused into the duodenum loop in iron-sufficient and iron-deficient rats. Total duodenal DMT1 and DMT1-IRE expression were increased during iron deficiency. After 15 min of 1 mg iron loading, the fluorescence intensity of duodenal DMT1 in iron-deficient rats was decreased and was comparable to that in iron-sufficient rats. Internalized DMT1-IRE as puncta was observed at 15 and 60 min after 1 mg iron loading, and the number of punctas was significantly increased after 60 min compared with control. There was no effect of 1 mg iron loading on the intracellular distribution of duodenal FPN. Our results suggest that the decrease and internalization of DMT1-IRE protein may be related, at least in part, to iron uptake suppression in SAMB.
Insights
A small iron dose induces a short-acting mucosal block (SAMB) in rats by reducing duodenal divalent metal transporter 1 (DMT1) protein levels. This mechanism transiently suppresses iron absorption without altering gene expression.
Area of Science:
- Physiology
- Nutritional Science
- Gastroenterology
Background:
- Oral iron administration can induce a mucosal block (MB), suppressing intestinal iron absorption.
- A recently identified short-acting mucosal block (SAMB) involves transient iron uptake suppression without gene changes, specific to iron-deficient rats.
- The roles of nonheme iron transporters, divalent metal transporter 1 (DMT1) and ferroportin (FPN), in SAMB remain unclear.
Purpose of the Study:
- To investigate the involvement of DMT1 and FPN in the transient suppression of iron uptake during SAMB.
- To elucidate the molecular mechanisms underlying SAMB in iron-deficient rats.
Main Methods:
- SAMB was induced by infusing 1 mg of iron into the duodenal loop of iron-sufficient and iron-deficient rats.
- Duodenal tissue was analyzed for DMT1 and FPN expression and intracellular distribution using fluorescence intensity and puncta imaging.
- Changes in DMT1-IRE protein levels and localization were assessed at 15 and 60 minutes post-iron loading.
Main Results:
- Iron deficiency increased total duodenal DMT1 and DMT1-IRE expression.
- Following 1 mg iron loading, duodenal DMT1 fluorescence intensity decreased in iron-deficient rats to levels similar to iron-sufficient rats.
- Internalization of DMT1-IRE into puncta increased significantly at 60 minutes post-iron loading; FPN intracellular distribution was unaffected.
Conclusions:
- The decrease and internalization of DMT1-IRE protein are likely involved in the iron uptake suppression observed in SAMB.
- SAMB represents a rapid, post-transcriptional regulatory mechanism for intestinal iron absorption.
- These findings highlight DMT1's dynamic regulation in response to luminal iron availability.
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