Harpreet Kaur Massaon and Pranav Kumar Prabhakar
Background: The intricate relationship between iron metabolism and diabetes mellitus has become a subject of increasing interest, with a growing body of evidence suggesting that iron plays a significant role in the pathophysiology of diabetes. Spe-cifically, the impact of iron on β-cell function has emerged as a critical area of study. Β cells, located in the pancreatic islets of Langerhans, are responsible for insulin synthesis and secretion.
Purpose: Understanding how iron influences these vital cells is crucial for unraveling the complexities of diabetes development and progression.
Methods: This review synthesizes current literature on the interaction between iron and β-cell function, exploring the molecular and cellular mechanisms underlying this relationship. We conducted a systematic search of databases, including PubMed and Scopus, to identify relevant studies published up to the present date. Articles were selected based on their focus on iron homeostasis, β-cell function, and their implica-tions for diabetes pathophysiology.
Results: Iron is an essential micronutrient that participates in various cellular pro-cesses, including energy metabolism and reactive oxygen species (ROS) regulation. In β cells, iron is intricately involved in insulin synthesis, folding, and maturation. However, an imbalance in iron homeostasis can lead to oxidative stress, mitochon-drial dysfunction, and impaired insulin secretion. The reviewed literature provides compelling evidence that alterations in iron levels can adversely affect β-cell func-tion, contributing to the development and progression of diabetes. Excess iron has been associated with increased oxidative stress within β cells, leading to damage and dysfunction.
Furthermore, iron-induced ROS may activate inflammatory pathways, promoting β-cell apoptosis and insulin resistance in peripheral tissues. Conversely, iron deficiency may also impact β-cell health.
Insufficient iron availability can com-promise the efficiency of insulin synthesis and secretion, potentially contributing to glucose dysregulation. Iron-deficient conditions may lead to alterations in cellular energy metabolism, further exacerbating the vulnerability of β cells to stressors.
Conclusions: Understanding the nuanced interplay between iron and β-cell function has implications for diabetes management. Therapeutic strategies aimed at modulating iron levels, such as iron chelation or dietary interventions, hold promise for preserving β-cell health and improving glycemic control. This review underscores the intricate relationship between iron and β-cell function, providing valuable insights into the pathophysiology of diabetes. Whether through excess or deficiency, iron significantly influences the health and function of β cells, shaping the landscape of diabetes development. Further research is warranted to delineate the precise mecha-nisms involved and to explore targeted interventions that may harness the therapeutic potential of modulating iron levels in diabetes management.
Afkhami-Ardekani, M., & Rashidi, M. (2009). Iron status in women with and without gestational diabetes mellitus. Journal of Diabetes and its Complications, 23(3), 194-198.
Anderson, C. P., Shen, M., Eisenstein, R. S., & Leibold, E. A. (2012). Mammalian iron metabolism and its control by iron regulatory proteins. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1823(9), 1468-1483.
Baker, K. S., Ness, K., Steinberger, J., Carter, A., Francisco, L., Burns, L., et al., (2005). Diabetes, Hypertension and Cardiovascular Events in Survivors of Hematopoietic Cell Transplantation (HCT): A Report from the Bone Marrow Transplant Survivor Study. Blood, 106(11), 699.
Beguin, Y. (2003). Soluble transferrin receptor for the evaluation of erythropoiesis and iron status. Clinica chimica acta, 329(1-2), 9-22.
D’Alessio, F., Hentze, M. W., & Muckenthaler, M. U. (2012). The hemochromatosis proteins HFE, TfR2, and HJV form a membrane-associated protein complex for hepcidin regulation. Journal of hepatology, 57(5), 1052-1060.
Dmochowski, KR., Finegood, D. T., Francombe, WI., Tyler, B., & Zinman, BE. (1993). Factors determining glucose tolerance in patients with thalassemia major. The Journal of Clinical Endocrinology & Metabolism, 77(2), 478-483.
Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D. A., Basava, A., et al., (1996). A novel MHC class I–like gene is mutated in patients with hereditary haemochromatosis. Nature genetics, 13(4), 399-408.
Fernández-Real, J. M., López-Bermejo, A., & Ricart, W. (2002). Cross-talk between iron metabolism and diabetes. Diabetes, 51(8), 2348-2354.
Fleming, D. J., Jacques, P. F., Tucker, K. L., Massaro, J. M., D’Agostino Sr, R. B., Wilson, P. W., & Wood, R. J. (2001). Iron status of the free-living, elderly Framingham Heart Study cohort: an iron-replete population with a high prevalence of elevated iron stores. The American journal of clinical nutrition, 73(3), 638-646.
Ford, E. S., & Cogswell, M. E. (1999). Diabetes and serum ferritin concentration among US adults. Diabetes care, 22(12), 1978-1983.
Gabrielsen, J. S., Gao, Y., Simcox, J. A., Huang, J., Thorup, D., Jones, D., et al., (2012). Adipocyte iron regulates adiponectin and insulin sensitivity. The Journal of clinical investigation, 122(10), 3529-3540.
Ganz, T., & Nemeth, E. (2009, October). Iron sequestration and anemia of inflammation. In Seminars in hematology (Vol. 46, No. 4, pp. 387-393). WB Saunders.
Hardie, D. G. (2011). AMP-activated protein kinase—an energy sensor that regulates all aspects of cell function. Genes & development, 25(18), 1895-1908.
Hatunic, M., Finucane, F. M., Norris, S., Pacini, G., & Nolan, J. J. (2010). Glucose metabolism after normalization of markers of iron overload by venesection in subjects with hereditary hemochromatosis. Metabolism, 59(12), 1811-1815.
Haurie, V., Boucherie, H., & Sagliocco, F. (2003). The Snf1 protein kinase controls the induction of genes of the iron uptake pathway at the diauxic shift in Saccharomyces cerevisiae. Journal of Biological Chemistry, 278(46), 45391-45396.
Hentze, M. W., Muckenthaler, M. U., Galy, B., & Camaschella, C. (2010). Two to tango: regulation of Mammalian iron metabolism. Cell, 142(1), 24-38.
Hostettler-Allen, R., Tappy, L., & Blum, J. W. (1993). Enhanced insulin-dependent glucose utilization in iron-deficient veal calves. The Journal of nutrition, 123(10), 1656-1667.
Hudson, D. M., Curtis, S. B., Smith, V. C., Griffiths, T. A., Wong, A. Y., Scudamore, et al., (2010). Human hephaestin expression is not limited to enterocytes of the gastrointestinal tract but is also found in the antrum, the enteric nervous system, and pancreatic β-cells. American Journal of Physiology-Gastrointestinal and Liver Physiology, 298(3), G425-G432.
Jomova, K., & Valko, M. (2011). Advances in metal-induced oxidative stress and human disease. Toxicology, 283(2-3), 65-87.
Koch, R. O., Zoller, H., Theurl, I., Obrist, P., Egg, G., Strohmayer, W. et al., (2003). Distribution of DMT 1 within the human glandular system. Histology and histopathology.2003;18:1095–1101.
Lowell, B. B., & Shulman, G. I. (2005). Mitochondrial dysfunction and type 2 diabetes. Science, 307(5708), 384-387.
McClain, D. A., Abraham, D., Rogers, J., Brady, R., Gault, P., Ajioka, R., & Kushner, J. P. (2006). High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis. Diabetologia, 49, 1661-1669.
Moirand, R., Adams, P. C., Bicheler, V., Brissot, P., & Deugnier, Y. (1997). Clinical features of genetic hemochromatosis in women compared with men. Annals of internal medicine, 127(2), 105-110.
Pietrangelo, A. (2010). Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology, 139(2), 393-408.
Prabhakar, P. K. (2020). Bacterial siderophores and their potential applications: a review. Current Molecular Pharmacology, 13(4), 295-305.
Prabhakar, P. K., Singh, K., Kabra, D., & Gupta, J. (2020). Natural SIRT1 modifiers as promising therapeutic agents for improving diabetic wound healing. Phytomedicine, 76, 153252.
Qiu, C., Zhang, C., Gelaye, B., Enquobahrie, D. A., Frederick, I. O., & Williams, M. A. (2011). Gestational diabetes mellitus in relation to maternal dietary heme iron and nonheme iron intake. Diabetes Care, 34(7), 1564-1569.
Rossetti, L., Giaccari, A., & DeFronzo, R. A. (1990). Glucose toxicity. Diabetes care, 13(6), 610-630.
Semenza, G. L. (2012). Hypoxia-inducible factors in physiology and medicine. Cell, 148(3), 399-408.
Sharifi, F., Nasab, N. M., & Zadeh, H. J. (2008). Elevated serum ferritin concentrations in prediabetic subjects. Diabetes and Vascular Disease Research, 5(1), 15-18.
Weatherall, D. J. (1998). 4 Pathophysiology of thalassaemia. Baillière’s clinical haematology, 11(1), 127-146.
| Periodicity | Biannually |
| Issue-1 | October |
| Issue-2 | April |
| ISSN Print | 2393-8536 |
| ISSN Online | 2393-8544 |
| RNI No. | CHAENG/2014/57978 |
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