Hepcidin is Directly Regulated by Insulin and Plays an Important Role in Iron Overload in Stz-Induced Diabetic Rats

  1. Min Li*
  1. Military Hygiene Department, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China
  1. *Corresponding Author: Min Li, Email: linlimin115{at}


Iron overload is frequently observed in type 2 diabetes mellitus (DM2) but the underlying mechanisms remains unclear. We hypothesize that hepcidin may be directly regulated by insulin and play an important role in iron overload in DM2.

We therefore examined the hepatic iron content, serum iron parameters, intestinal iron absorption and liver hepcidin expression in rats treated with streptozotocin (STZ) which was given alone or after a high-fat diet induced insulin resistance. The direct effect of insulin on hepcidin and its molecular mechanisms were furthermore determined in vitro in HepG2 cells.

STZ administration caused a significant reduction in liver hepcidin level and a marked increase in intestinal iron absorption, serum iron and hepatic iron content. Insulin obviously up-regulated hepcidin expression in HepG2 cells and enhanced STAT3 protein synthesis and DNA binding activity. The effect of insulin on hepcidin disappeared when STAT3 pathway was blocked, and could be partially inhibited by U0126.

In conclusion, the present study suggests that hepcidin can be directly regulated by insulin and the suppressed liver hepcidin synthesis may be an important reason of the iron overload in DM2.

  • Received August 11, 2013.
  • Accepted December 23, 2013.

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