Normal Iron In Diabetes

[ironjustice]

"Iron exerts detrimental effects on β-cell function"

Dietary iron restriction or iron chelation protects from diabetes and
loss of β-cell function in the obese (ob/ob lep-/-) mouse
Am J Physiol Endocrinol Metab. 2010 June; 298(6): E1236-E1243.
Published online 2010 March 30.
Robert C. Cooksey,1,2,* Deborah Jones,1,* Scott Gabrielsen,1 Jingyu
Huang,1 Judith A. Simcox,1 Bai Luo,1 Yudi Soesanto,1 Hugh Rienhoff,3,4
E. Dale Abel,1 and Donald A. McClain1,2
1Departments of Medicine and Biochemistry, University of Utah School
of Medicine
2Veterans Affairs Medical Center, Research Service, Salt Lake City,
Utah;
3FerroKin BioSciences, San Carlos
4The Children's Hospital Oakland Research Institute, Oakland,
California
Address for reprint requests and other correspondence: D. A. McClain,
Div. of Endocrinology, 30 N. 2030 East, Salt Lake City, UT 84132 (e-
mail: Donald....@hsc.utah.edu).
Received January 8, 2010; Accepted March 28, 2010.

Abstract.
Iron overload can cause insulin deficiency, but in some cases this may
be insufficient to result in diabetes.
We hypothesized that the protective effects of decreased iron would be
more significant with increased β-cell demand and stress.
Therefore, we treated the ob/ob mouse model of type 2 diabetes with an
iron-restricted diet (35 mg/kg iron) or with an oral iron chelator.
Control mice were fed normal chow containing 500 mg/kg iron.
Neither treatment resulted in iron deficiency or anemia.
The low-iron diet significantly ameliorated diabetes in the mice.
The effect was long lasting and reversible.
Ob/ob mice on the low-iron diet exhibited significant increases in
insulin sensitivity and β-cell function, consistent with the phenotype
in mouse models of hereditary iron overload.
The effects were not accounted for by changes in weight or feeding
behavior.
Treatment with iron chelation had a more dramatic effect, allowing the
ob/ob mice to maintain normal glucose tolerance for at least 10.5 wk
despite no effect on weight.
Although dietary iron restriction preserved β-cell function in ob/ob
mice fed a high-fat diet, the effects on overall glucose levels were
less apparent due to a loss of the beneficial effects of iron on
insulin sensitivity.
Beneficial effects of iron restriction were minimal in wild-type mice
on normal chow but were apparent in mice on high-fat diets.
We conclude that, even at "normal" levels, iron exerts detrimental
effects on β-cell function that are reversible with dietary
restriction or pharmacotherapy.

Keywords: insulin secretion, type 2 diabetes

doi: 10.1152/ajpendo.00022.2010

PMCID: PMC2886527

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2886527/

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