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      Serum ferritin as a risk factor for type 2 diabetes mellitus, regulated by liver transferrin receptor 2

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          Abstract

          Objective

          The aim of this study was to evaluate the effect of TFR2 on iron storage in type 2 diabetes.

          Methods

          A cross-sectional study was conducted among 1938 participants from the Jiangchuan Community of Shanghai. A total of 784 participants with T2DM and 1154 normal participants (non-T2DM) were enrolled in this study. Serum ferritin, fasting blood glucose, postprandial blood glucose, and HbA1C (glycated hemoglobin A1c) levels were determined. Eighteen Wistar male rats were randomly assigned into three groups ( n = 6/group): rats in a high-fat diet streptozotocin (HFD+STZ) group were fed with HFD for 4 weeks and intraperitoneally injected with streptozotocin (STZ); rats in a control group were fed with a standard diet for 4 weeks and intraperitoneally injected with buffer; rats in an STZ group were fed with a standard diet for 4 weeks and intraperitoneally injected with streptozotocin. Glucose tolerance test was performed at the end of the study. Blood samples and liver tissues were assessed for liver TFR2, blood glucose, serum ferritin, and iron levels.

          Results

          The mean serum ferritin level of T2DM participants was significantly higher than that of the control group (227 (140–352) vs 203.5 (130.5–312) ng/mL, P < 0.05). Serum ferritin level was an independent risk factor for T2DM (high ferritin group vs low ferritin group, 1.304 (1.03–1.651), P < 0.05). Diabetic rats showed reduced liver TFR2 levels, with increased serum ferritin levels.

          Conclusion

          T2DM participants exhibited iron disorder with elevated serum ferritin levels. Elevated serum ferritin levels in diabetic rats were accompanied by reduced liver TFR2 levels.

          Related collections

          Most cited references26

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          Two to tango: regulation of Mammalian iron metabolism.

          Disruptions in iron homeostasis from both iron deficiency and overload account for some of the most common human diseases. Iron metabolism is balanced by two regulatory systems, one that functions systemically and relies on the hormone hepcidin and the iron exporter ferroportin, and another that predominantly controls cellular iron metabolism through iron-regulatory proteins that bind iron-responsive elements in regulated messenger RNAs. We describe how the two distinct systems function and how they "tango" together in a coordinated manner. We also highlight some of the current questions in mammalian iron metabolism and discuss therapeutic opportunities arising from a better understanding of the underlying biological principles. Copyright 2010 Elsevier Inc. All rights reserved.
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            Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.

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              The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22.

              Haemochromatosis is a common recessive disorder characterized by progressive iron overload, which may lead to severe clinical complications. Most patients are homozygous for the C282Y mutation in HFE on 6p (refs 1-5). A locus for juvenile haemochromatosis (HFE2) maps to 1q (ref. 7). Here we report a new locus (HFE3) on 7q22 and show that a homozygous nonsense mutation in the gene encoding transferrin receptor-2 (TFR2) is found in people with haemochromatosis that maps to HFE3.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                02 November 2021
                01 December 2021
                : 10
                : 12
                : 1513-1521
                Affiliations
                [1 ]Department of Endocrinology , Shanghai Fifth People’s Hospital affiliated to Fudan University, Minhang District, Shanghai, People’s Republic of China
                Author notes
                Correspondence should be addressed to S Zang or J Liu: sophiazsf@ 123456fudan.edu.cn or liu__jun@ 123456fudan.edu.cn
                Article
                EC-21-0316
                10.1530/EC-21-0316
                8679876
                34727090
                928a020f-546b-49d7-b714-658306d4d82b
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 10 October 2021
                : 02 November 2021
                Categories
                Research

                type 2 diabetes,serum ferritin,transferrin receptor 2

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