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Iron stimulates insulin secretion in clonal pancreatic β‐cells and dissociated rat islets
Author(s) -
Erion Karel Arnt,
Ferrante Tom,
Corkey Barbara,
Deeney Jude
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1010.13
Subject(s) - medicine , endocrinology , pancreatic islets , lipolysis , reactive oxygen species , basal (medicine) , insulin , transferrin , chemistry , glucose homeostasis , diabetes mellitus , secretion , islet , biology , insulin resistance , biochemistry , adipose tissue
Dysregulation of iron homeostasis as observed in people with hemochromatosis and is associated with an increased risk of developing type II diabetes mellitus (T2DM). Also it has recently been shown that dietary iron restriction or iron chelation can prevent the development of diabetes in mouse models of obesity. Our goal was to determine the role of iron in the process of insulin secretion. Clonal pancreatic β‐cells (INS‐1 832/13) and dissociated rat islets were incubated in increasing concentrations of holotransferrin or iron citrate for 1–2 hours. Additionally, perifusions were performed on INS‐1 and whole rat islets. Insulin secretion (HTRF), lipolysis (glycerol release), O 2 consumption (seahorse), reactive oxygen species (2′,7′‐Dichlorofluorescein), and PKC activity (MARKS protein) were all measured. Acute exposure of INS‐1 and dissociated rat islets to transferrin bound iron and cell permeable iron salts increases both basal and glucose stimulated insulin secretion (GSIS). This effect is transient and is readily reversible if cells are given a recovery period or are treated with an antioxidant. Acute exposure of both INS‐1 and dissociated rat islets to iron readily increases reactive oxygen species (ROS) which can be blocked using an antioxidant. Iron also increases PKC activity and increases lipolysis in β‐cells. Exposure to iron quickly and reversibly increases both basal and GSIS via a ROS dependent mechanism. Increased PKC activity and lipolysis may play a primary role in this effect. Funding provided by the National Institutes of Health (NIH)