Diabetes in HFE Hemochromatosis

Table 2

Proposed roles of iron in type 2 diabetes.

Variable	Mechanism	Reference
Body iron status	Modulates transcription, membrane expression/affinity of insulin receptor expression in hepatocytes, influences insulin-dependent gene expression	[191]
Dietary iron	Controls circadian hepatic glucose metabolism through heme synthesis	[192]
Intake of processed meat, red meat	Higher risk of type 2 diabetes	[161, 193, 194]
Dietary iron restriction, iron chelation	Increased insulin sensitivity, beta-cell function (ob/ob lep^−/− mice)	[195]
Iron chelation	Ameliorates adipocyte hypertrophy via suppression of oxidative stress, inflammatory cytokines, and macrophage infiltration	[196]
Starvation	Increased liver Pck1 transcription, hepcidin expression, and degradation of ferroportin; hypoferremia, hepatic iron retention (C57BL/6Crl, 129S2/SvPas, BALB/c, and Creb3l3^−/− null mice)	[197]
High fat diet	Increased hepatic iron regulatory protein-1, increased transferrin receptor 1 expression, increased hepcidin, decreased ferroportin (Hfe^−/− mice); increased fatty acid oxidation, hypermetabolism, elevated hepatic glucose production (Hfe^−/− mice)	[198, 199]
Cellular iron uptake	Stimulated by insulin	[200]
Excess hepatic iron	Hyperinsulinemia due to decreased insulin extraction, impaired insulin secretion	[121]
Iron-related proteins in adipose tissue	Expression modulated by insulin resistance	[201]
Adipocyte iron	Regulates leptin and food intake	[202]
Adiponectin	Transcription negatively regulated by iron	[203, 204]
Visfatin	Positive association with serum prohepcidin, negative correlation with serum soluble transferrin receptor in men with altered glucose tolerance	[205]
Heme oxygenase-1 promoter microsatellite polymorphism	Higher ferritin with short (GT)() repeats	[206]
Antioxidants	Lower levels partially explained by iron alterations	[207]