Hepcidin levels in diabetes mellitus and polycystic ovary syndrome
Amir H Sam,Mark Busbridge,Anjali Amin,L Webber,Davinia White,Stephen Franks,Niamh M. Martin,Michelle L. Sleeth,Nurhafzan A. Ismail,N. Mat Daud,Dimitris Papamargaritis,C. W. le Roux,Richard Chapman,Gary Frost,Stephen R. Bloom,Kevin Murphy +15 more
TLDR
It is hypothesized that individuals with insulin resistance have inadequate hepcidin levels for their iron load, and these levels may be related to insulin resistance.Abstract:
Aim
Increased body iron is associated with insulin resistance. Hepcidin is the key hormone that negatively regulates iron homeostasis. We hypothesized that individuals with insulin resistance have inadequate hepcidin levels for their iron load.
Methods
Serum concentrations of the active form of hepcidin (hepcidin-25) and hepcidin:ferritin ratio were evaluated in participants with Type 2 diabetes (n = 33, control subjects matched for age, gender and BMI, n = 33) and participants with polycystic ovary syndrome (n = 27, control subjects matched for age and BMI, n = 16). To investigate whether any changes observed were associated with insulin resistance rather than insulin deficiency or hyperglycaemia per se, the same measurements were made in participants with Type 1 diabetes (n = 28, control subjects matched for age, gender and BMI, n = 30). Finally, the relationship between homeostasis model assessment of insulin resistance and serum hepcidin:ferritin ratio was explored in overweight or obese participants without diabetes (n = 16).
Results
Participants with Type 2 diabetes had significantly lower hepcidin and hepcidin:ferritin ratio than control subjects (P < 0.05 and P < 0.01, respectively). Participants with polycystic ovary syndrome had a significantly lower hepcidin:ferritin ratio than control subjects (P < 0.05). There was no significant difference in hepcidin or hepcidin:ferritin ratio between participants with Type 1 diabetes and control subjects (P = 0.88 and P = 0.94). Serum hepcidin:ferritin ratio inversely correlated with homeostasis model assessment of insulin resistance (r = –0.59, P < 0.05).
Conclusion
Insulin resistance, but not insulin deficiency or hyperglycaemia per se, is associated with inadequate hepcidin levels. Reduced hepcidin concentrations may cause increased body iron stores in insulin-resistant states.read more
Citations
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Iron and liver fibrosis: Mechanistic and clinical aspects.
TL;DR: The role of iron is described in various clinical pathologies, the significance and potential of iron-related proteins in the diagnosis and therapeutics of liver fibrosis are highlighted and the underlying mechanisms by which excess iron can facilitate fibrotic responses are examined.
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Hepcidin Is Directly Regulated by Insulin and Plays an Important Role in Iron Overload in Streptozotocin-Induced Diabetic Rats
TL;DR: The current study suggests that hepcidin can be directly regulated by insulin, and the suppressed liver hePCidin synthesis may be an important reason for the iron overload in DM2.
Journal ArticleDOI
Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease.
Sanne van Raaij,Rachel P. L. van Swelm,Karlijn Bouman,Maaike Cliteur,Marius C. van den Heuvel,Jeanne Pertijs,Dominic Patel,Paul Bass,Harry van Goor,Robert J. Unwin,Robert J. Unwin,Surjit K. S. Srai,Dorine W. Swinkels +12 more
TL;DR: Iron deposition is relatively common in CKD, and may result from altered molecular iron handling and may contribute to renal injury, as indicated by heme oxygenase-1 abundance.
Journal ArticleDOI
Unbiased RNAi screen for hepcidin regulators links hepcidin suppression to proliferative Ras/RAF and nutrient-dependent mTOR signaling
Katarzyna Mleczko-Sanecka,Franziska Roche,Ana Rita da Silva,Debora Call,Flavia D’Alessio,Anan Ragab,Philip E. Lapinski,Ramesh Ummanni,Ulrike Korf,Christopher C. Oakes,Georg Damm,Lorenza A. D'Alessandro,Ursula Klingmüller,Philip D. King,Michael Boutros,Matthias W. Hentze,Martina U. Muckenthaler +16 more
TL;DR: Links between the control of systemic iron homeostasis and critical liver processes such as regeneration, response to injury, carcinogenesis, and nutrient metabolism are identified using a combination of RNAi screening, reverse phase protein arrays, and small molecules testing.
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Anaemia, a common but often unrecognized risk in diabetic patients: A review
A. Angelousi,Etienne Larger +1 more
TL;DR: Screening for autoimmune gastritis, pernicious anaemia, Hashimoto's thyroiditis, coeliac disease and Addison's disease is recommended, and screening for rare causes of anaemia should be suspected in young patients or when the classical causes are excluded.
References
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Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome
TL;DR: Since the 1990 NIH-sponsored conference on polycystic ovary syndrome, it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria.
Journal ArticleDOI
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Elizabeta Nemeth,Marie S. Tuttle,Julie Powelson,Michael B. Vaughn,Adriana Donovan,Diane M. Ward,Tomas Ganz,Jerry Kaplan +7 more
TL;DR: It is reported that hepcidin bound to ferroportin in tissue culture cells, leading to decreased export of cellular iron and the posttranslational regulation of ferroports by hePCidin may complete a homeostatic loop.
Journal ArticleDOI
Men at risk: occupation and male infertility☆
TL;DR: There is accumulating evidence that workplace exposure to toxic substances contributes to male infertility, and men suffering from infertility problems may do well to look at their occupations, where exposure to certain substances may be a contributory factor.
Journal ArticleDOI
Hepcidin, a Urinary Antimicrobial Peptide Synthesized in the Liver *
TL;DR: Hepcidin may be a vertebrate counterpart of cysteine-rich antimicrobial peptides produced in the fat body of insects and exhibited antifungal activity against Candida albicans, Aspergillus fumigatus, and As pergillus nigerand antibacterial activity against Escherichia coli.
Journal ArticleDOI
A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload
Christelle Pigeon,Gennady Ilyin,Brice Courselaud,Patricia Leroyer,Bruno Turlin,Pierre Brissot,Olivier Loréal +6 more
TL;DR: The data strongly suggest that the product of the new liver-specific gene HEPC might play a specific role during iron overload and exhibit additional functions distinct from its antimicrobial activity.