title: Glucose metabolism in the Belgrade rat, a model of iron-loading anemia.
abstract: The iron-diabetes hypothesis proposes an association between iron overload and glucose metabolism that is supported by a number of epidemiological studies. The prevalence of type 2 diabetes in patients with hereditary hemochromatosis and iron-loading thalassemia supports this hypothesis. The Belgrade rat carries a mutation in the iron transporter divalent metal transporter 1 (DMT1) resulting in iron-loading anemia. In this study, we characterized the glycometabolic status of the Belgrade rat. Belgrade rats displayed normal glycemic control. Insulin signaling and secretion were not impaired, and pancreatic tissue did not incur damage despite high levels of nonheme iron. These findings suggest that loss of DMT1 protects against oxidative damage to the pancreas and helps to maintain insulin sensitivity despite iron overload. Belgrade rats had lower body weight but increased food consumption compared with heterozygous littermates. The unexpected energy balance was associated with increased urinary glucose output. Increased urinary excretion of electrolytes, including iron, was also observed. Histopathological evidence suggests that altered renal function is secondary to changes in kidney morphology, including glomerulosclerosis. Thus, loss of DMT1 appears to protect the pancreas from injury but damages the integrity of kidney structure and function.
authors.affiliation: Department of Genetics & Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Xuming
authors.initials: X
authors.lastname: Jia
authors.forename: Jonghan
authors.initials: J
authors.lastname: Kim
authors.forename: Tania
authors.initials: T
authors.lastname: Veuthey
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Lee
authors.forename: Marianne
authors.initials: M
authors.lastname: Wessling-Resnick
mesh_terms: D000756:Anemia, Sideroblastic / Q000151:congenital* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics; D004195:Disease Models, Animal; D018149:Glucose Intolerance; D006029:Glycosuria / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000378:metabolism; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism; D018384:Oxidative Stress; D010179:Pancreas / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011922:Rats, Mutant Strains; D015398:Signal Transduction; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D001786:Blood Glucose; D027682:Cation Transport Proteins; D007328:Insulin; D007501:Iron; D000099236:Solute Carrier Family 11, Member 2
keywords: iron overload; kidney