PMID- 18755804
OWN - NLM
STAT- MEDLINE
DCOM- 20081126
LR  - 20211020
IS  - 0193-1857 (Print)
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Linking)
VI  - 295
IP  - 4
DP  - 2008 Oct
TI  - Interrelationships between circulating gastrin and iron status in mice and 
      humans.
PG  - G855-61
LID - 10.1152/ajpgi.90359.2008 [doi]
AB  - The observations that the peptide hormone gastrin interacts with transferrin in 
      vitro and that circulating gastrin concentrations are increased in the 
      iron-loading disorder hemochromatosis suggest a possible link between gastrin and 
      iron homeostasis. This study tested the hypothesis that gastrin and iron status 
      are interrelated by measurement of iron homeostasis in mice and humans with 
      abnormal circulating gastrin concentrations. Intestinal iron absorption was 
      determined by (59)Fe uptake following oral gavage, and concentrations of duodenal 
      divalent metal transporter-1 (DMT-1) and hepatic hepcidin mRNAs were determined 
      by quantitative real-time PCR in agastrinemic (GasKO), hypergastrinemic 
      cholecystokinin 2 receptor-deficient (CCK2RKO), or wild-type mice. Iron status 
      was measured by standard methods in the same mice and in hypergastrinemic humans 
      with multiple endocrine neoplasia type 1 (MEN-1). Iron absorption was increased 
      sixfold and DMT-1 mRNA concentration fourfold, and transferrin saturation was 
      reduced 0.8-fold and hepcidin mRNA expression 0.5-fold in juvenile GasKO mice 
      compared with age-matched wild-type mice. In mature mice, few differences were 
      observed between the strains. Juvenile CCK2RKO mice were hypergastrinemic and had 
      a 5.4-fold higher DMT-1 mRNA concentration than wild-type mice without any 
      increase in iron absorption. In contrast to juvenile GasKO mice, juvenile CCK2RKO 
      mice had a 1.5-fold greater transferrin saturation, which was reflected in a 
      twofold increase in liver iron deposition at maturity compared with wild-type 
      mice. The correlation between transferrin saturation and circulating gastrin 
      concentration observed in mutant mice was also observed in human patients with 
      MEN, in whom hypergastrinemia correlated positively (P = 0.004) with an increased 
      transferrin saturation. Our data indicate that, in juvenile animals when iron 
      demand is high, circulating gastrin concentrations may alter iron status by a 
      CCK2R-independent mechanism.
FAU - Kovac, Suzana
AU  - Kovac S
AD  - Univ. of Melbourne Dept. of Surgery, Austin Health, Studley Rd., Heidelberg, 
      Victoria 3084, Australia.
FAU - Smith, Kelly
AU  - Smith K
FAU - Anderson, Gregory J
AU  - Anderson GJ
FAU - Burgess, John R
AU  - Burgess JR
FAU - Shulkes, Arthur
AU  - Shulkes A
FAU - Baldwin, Graham S
AU  - Baldwin GS
LA  - eng
GR  - R01 GM065926/GM/NIGMS NIH HHS/United States
GR  - R01 GM065926-06/GM/NIGMS NIH HHS/United States
GR  - GM065926/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080828
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (Cation Transport Proteins)
RN  - 0 (Gastrins)
RN  - 0 (HAMP protein, human)
RN  - 0 (Hamp protein, mouse)
RN  - 0 (Hepcidins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Cholecystokinin B)
RN  - 0 (solute carrier family 11- (proton-coupled divalent metal ion transporters), 
      member 2)
RN  - 9007-73-2 (Ferritins)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Animals
MH  - Antimicrobial Cationic Peptides/metabolism
MH  - Cation Transport Proteins/metabolism
MH  - Duodenum/metabolism
MH  - Female
MH  - Ferritins/blood
MH  - Gastrins/*blood
MH  - Hepcidins
MH  - Homeostasis
MH  - Humans
MH  - Iron/*blood
MH  - Liver/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/blood
MH  - RNA, Messenger/metabolism
MH  - Receptor, Cholecystokinin B/deficiency/*physiology
PMC - PMC2575913
EDAT- 2008/08/30 09:00
MHDA- 2008/12/17 09:00
PMCR- 2009/10/01
CRDT- 2008/08/30 09:00
PHST- 2008/08/30 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/08/30 09:00 [entrez]
PHST- 2009/10/01 00:00 [pmc-release]
AID - ajpgi.90359.2008 [pii]
AID - GI-90359-2008 [pii]
AID - 10.1152/ajpgi.90359.2008 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2008 Oct;295(4):G855-61. doi: 
      10.1152/ajpgi.90359.2008. Epub 2008 Aug 28.