RGD Reference Report - Hyperinsulinemia induces hepatic iron overload by increasing liver TFR1 via the PI3K/IRP2 pathway. - Rat Genome Database

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Hyperinsulinemia induces hepatic iron overload by increasing liver TFR1 via the PI3K/IRP2 pathway.

Authors: Jiang, Xin  Wang, Heyang  Shi, Wencai  Shen, Zhilei  Shen, Hui  Li, Min 
Citation: Jiang X, etal., J Mol Endocrinol. 2014 Dec;53(3):381-92. doi: 10.1530/JME-14-0122.
RGD ID: 12903966
Pubmed: PMID:25385842   (View Abstract at PubMed)
DOI: DOI:10.1530/JME-14-0122   (Journal Full-text)

Dysmetabolic iron overload syndrome (DIOS) is frequently observed, but the underlying mechanism remains unclear. We propose the hypothesis that hyperinsulinemia, a common characteristic of DIOS, may stimulate liver transferrin receptor 1 (TFR1) expression via the PI3K/iron regulatory protein 2 (IRP2) pathway, leading to the occurrence of DIOS. The hepatic iron content, serum iron parameters, and expressions of TFRs and IRPs in the liver were determined in rats with temporary or long-lasting hyperinsulinemia induced by acute or chronic administration of insulin. The effect of insulin on TFR1 expression and its molecular mechanism were determined in HL-7702 cells in vitro. It was found that long-lasting hyperinsulinemia significantly increased TFR1 expression in the liver and induced mild-to-moderate hepatic iron overload, which was accompanied by a normal level of serum iron. Insulin markedly upregulated both protein and mRNA levels of TFR1 in HL-7702 cells. The stability of TFR1 mRNA stability, together with expression of IRPs expression, were both significantly increased by insulin treatment. Insulin-induced TFR1 expression was blocked by IRP2, but not by IRP1 interference, and disappeared when HL-7702 cells were pretreated with LY294002, triciribine hydrate, or rapamycin. In conclusion, the findings of this study indicate that hyperinsulnemia could induce hepatic iron overload by upregulating liver TFR1 via the PI3K/AKT/mTOR/IRP2 pathway, which may be one of the main reasons for the occurrence of DIOS.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IREB2Humanhyperinsulinism  ISOIreb2 (Rattus norvegicus)protein:increased expression:liver (rat)RGD 
Ireb2Rathyperinsulinism  IEP protein:increased expression:liver (rat)RGD 
Ireb2Mousehyperinsulinism  ISOIreb2 (Rattus norvegicus)protein:increased expression:liver (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ireb2  (iron responsive element binding protein 2)

Genes (Mus musculus)
Ireb2  (iron responsive element binding protein 2)

Genes (Homo sapiens)
IREB2  (iron responsive element binding protein 2)


Additional Information