title: Iron Regulation of Pancreatic Beta-Cell Functions and Oxidative Stress.
abstract: Dietary advice is the cornerstone in first-line treatment of metabolic diseases. Nutritional interventions directed at these clinical conditions mainly aim to (a) improve insulin resistance by reducing energy-dense macronutrient intake to obtain weight loss and (b) reduce fluctuations in insulin secretion through avoidance of rapidly absorbable carbohydrates. However, even in the majority of motivated patients selected for clinical trials, massive efforts using this approach have failed to achieve lasting efficacy. Less attention has been given to the role of micronutrients in metabolic diseases. Here, we review the evidence that highlights (a) the importance of iron in pancreatic beta-cell function and dysfunction in diabetes and (b) the integrative pathophysiological effects of tissue iron levels in the interactions among the beta cell, gut microbiome, hypothalamus, innate and adaptive immune systems, and insulin-sensitive tissues. We propose that clinical trials are warranted to clarify the impact of dietary or pharmacological iron reduction on the development of metabolic disorders.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark; email: tmpo@sund.ku.dk.
authors.forename: Marie Balslev
authors.initials: MB
authors.lastname: Backe
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark; email: tmpo@sund.ku.dk.
authors.forename: Ingrid Wahl
authors.initials: IW
authors.lastname: Moen
authors.affiliation: Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts 02115.
authors.forename: Christina
authors.initials: C
authors.lastname: Ellervik
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark; email: tmpo@sund.ku.dk.
authors.forename: Jakob Bondo
authors.initials: JB
authors.lastname: Hansen
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark; email: tmpo@sund.ku.dk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mandrup-Poulsen
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017209:Apoptosis; D003920:Diabetes Mellitus / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D019587:Dietary Supplements / Q000009:adverse effects; D019317:Evidence-Based Medicine; D000069196:Gastrointestinal Microbiome / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D007031:Hypothalamus / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019190:Iron Overload / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019266:Iron, Dietary / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism
chemical_list: D007328:Insulin; D019266:Iron, Dietary; D017382:Reactive Oxygen Species
keywords: apoptosis; diabetes; insulin secretion; metabolism; metal ion transport; mitochondrial stress; reactive oxygen species