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Title: Interrelationships between circulating gastrin and iron status in mice and humans.
Austin Authors: Kovac, Suzana;Smith, Kelly;Anderson, Gregory J;Burgess, John R;Shulkes, Arthur;Baldwin, Graham S
Affiliation: Univ. of Melbourne Dept. of Surgery, Austin Health, Studley Rd., Heidelberg, Victoria 3084, Australia
Issue Date: 28-Aug-2008
Publication information: American Journal of Physiology. Gastrointestinal and Liver Physiology 2008; 295(4): G855-61
Abstract: 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.
Gov't Doc #: 18755804
DOI: 10.1152/ajpgi.90359.2008
Type: Journal Article
Subjects: Animals
Antimicrobial Cationic Peptides.metabolism
Cation Transport Proteins.metabolism
Mice, Knockout
Middle Aged
Multiple Endocrine Neoplasia Type 1.blood
RNA, Messenger.metabolism
Receptor, Cholecystokinin B.deficiency.physiology
Appears in Collections:Journal articles

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