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Interrelationships between circulating gastrin and iron status in mice and humans.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kovac, Suzana Smith, Kelly Anderson, Gregory J. Burgess, John R. Shulkes, Arthur Baldwin, Graham S.
Description	Country affiliation: Australia Author Affiliation: Kovac S ( Univ. of Melbourne Dept. of Surgery, Austin Health, Studley Rd., Heidelberg, Victoria 3084, Australia.)
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.
File Format	HTM / HTML
ISSN	01931857
e-ISSN	15221547
DOI	10.1152/ajpgi.90359.2008
Journal	AJP: Gastrointestinal and Liver Physiology
Issue Number	4
Volume Number	295
Language	English
Publisher	American Physiological Society
Publisher Date	2008-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Physiology Discipline Gastroenterology Gastrins Blood Receptor, Cholecystokinin B Physiology Animals Antimicrobial Cationic Peptides Metabolism Cation Transport Proteins Duodenum Ferritins Hepcidins Homeostasis Liver Mice Mice, Knockout Multiple Endocrine Neoplasia Type 1 Rna, Messenger Deficiency Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Hepatology Physiology Physiology (medical) Gastroenterology

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