Part 5: Beta Cell Fragility in an Iron-Loaded Terrain
- Bowie Matteson
- 1 day ago
- 18 min read
How systemic overload becomes local destruction
By now, you’ve followed iron from its vital role in human metabolism to its destructive potential when left unregulated.
In Part 1, we traced iron’s essential functions — from oxygen transport and ATP production to DNA synthesis — and the tightly choreographed systems that keep it in balance.
Part 2 dove into the nature of inflammation itself, exploring how reactive oxygen species (ROS) serve as both defense and danger depending on the context.
Part 3 connected the dots between these two worlds, showing how iron transforms stable ROS into volatile cellular threats, setting the stage for metabolic breakdown.
And in Part 4, we zoomed out — examining how iron imbalance disrupts multiple body systems: the liver, gut, immune system, brain, endocrine network, and bone — each one tipping the terrain closer to chronic illness.
Now, we arrive at the final frontier of metabolic vulnerability: the pancreatic beta cell.
Though small in number and size, beta cells are the body’s ultimate glucose gatekeepers — dynamically responding to blood sugar changes and releasing insulin with incredible precision. But this constant metabolic performance comes with a steep cost: high oxygen demand, high mitochondrial output, and almost no antioxidant reserve.
In this fragile microenvironment, even mild iron dysregulation can become catastrophic.
This chapter explores how the iron burden that builds across systems eventually converges on the beta cell — not as a random accident, but as a final domino in a long chain of terrain-wide compensations. We’ll unpack:
Why beta cells are iron-sensing sentinels, producing hepcidin while lacking the usual defenses against oxidative damage
How iron-induced ferroptosis and insulin resistance compromise insulin production and signaling
The genetic landscape where iron-regulatory and diabetes-risk genes intersect
And whether beta cell failure is a root cause or a last casualty in the slow unraveling of metabolic harmony
Ultimately, this chapter will give you new eyes to see diabetes — not as an isolated diagnosis, but as a culmination of systemic iron mismanagement and missed opportunities for course correction.
🔁 1. The Beta Cell as an Iron-Sensitive Metabolic Sensor
To regulate blood sugar is to regulate energy. To regulate energy is to regulate iron.
The pancreatic beta cell is a master interpreter of metabolic context — reading the bloodstream like a code, sensing nutrient signals, and releasing insulin in precisely timed pulses. Its primary task may be glucose regulation, but underneath that lies a far older evolutionary function: energy surveillance. And no mineral is more central to cellular energy than iron.
Unlike other islet cells, the beta cell uniquely expresses hepcidin, the body’s primary iron-regulatory hormone. This is not a random quirk — it’s a clue to the cell’s ancient role as an iron-sensitive metabolic sensor. Hepcidin controls ferroportin, the iron exporter found on cell surfaces, determining whether iron stays inside or gets released into circulation. That means beta cells are not just metabolically active — they are gatekeepers of iron traffic.
This makes sense when we consider the energetic demands of insulin production. To release insulin, beta cells rely on:
Rapid mitochondrial ATP generation
Calcium-dependent vesicle trafficking
Glucose oxidation and redox-sensitive signaling cascades
All of these processes require iron as a cofactor or catalyst — particularly within the mitochondria. Beta cells are some of the most mitochondria-dense cells in the body, second only to neurons and cardiac cells. More mitochondria means more iron. More iron means more reactive oxygen species. And yet, beta cells are uniquely vulnerable to that very byproduct.
🧬 Why would a pancreatic beta cell care about iron?
Because insulin release is metabolically expensive, and iron is essential for ATP production via mitochondrial oxidative phosphorylation.
Hepcidin expression allows the beta cell to sense, fine-tune, and suppress local iron influx when oxidative load gets too high.
It’s a feedback governor, meant to protect the cell from the very spark it requires to function.
In evolutionary terms, this hepcidin expression may have emerged as a safety valve for redox management. Beta cells are metabolically brilliant—but only if they can survive the very combustion they rely on.
The impending metabolic activity tied to glucose consumption makes beta cells a sentinel in aligning all of the materials necessary to process sugar efficiently.
🗣️ Glucose coming in? Mobilize iron in the beta cell mitochondria to ensure there is enough to fuel the increased insulin production.
➡️ Increased insulin production? Glucose is going to be entering cells. We'll need iron available for the body's mitochondria to properly utilize the incoming energy.
~And after a meal~
🛑 No more glucose coming in? Decreased insulin production? Signal iron's uptake via the hepcidin/ferroportin axis to avoid any unnecessary exposure and reactivity with surrounding tissues and ROS.
This may help explain why beta cells are disproportionately affected by inflammation when compared to the rest of the islet cell types. Why wouldn't alpha cells and delta cells take on the same inflammatory onslaught that beta cells would? Perhaps because of the beta cell's uniquely intimate relationship with iron.
🔬 2. High Mitochondrial Density = High Iron Vulnerability
Most cells come prepared with antioxidant defenses — superoxide dismutase (SOD), catalase, glutathione peroxidase, and peroxiredoxins — to disarm the ROS created during energy metabolism.
Beta cells, however, are remarkably poor in these enzymes.
Beta cells are mitochondrial powerhouses, but unlike muscle or liver cells, they lack robust antioxidant defenses. That makes mitochondria in beta cells:
🚧 Iron-dense (due to their role in heme, Fe-S clusters, and respiratory complexes)
⚠️ ROS-prone (especially when iron is not buffered or properly compartmentalized)
🧨 Fenton-capable zones where hydrogen peroxide can rapidly transform into the destructive hydroxyl radical
Their antioxidant reserves are minimal, making them highly susceptible to oxidative damage even under normal physiological stress. In an environment of systemic inflammation or iron overload, this vulnerability escalates rapidly — triggering:
Lipid peroxidation
Mitochondrial fragmentation
Insulin secretion failure
And eventually, ferroptosis — a type of iron-induced cell death
This creates a paradox:
The very organelles enabling insulin secretion also lay the groundwork for its destruction under conditions of chronic stress.
Far from a freak occurrence, this appears to be a conserved tradeoff: metabolic brilliance at the cost of redox fragility.
This seeming self-sabotage by beta cells, making more ROS in a high-iron environment, highlights the systemic deficits leading to beta cell failure. As we explored in Part 3, beta cell fragility is not a design defect, it illustrates how each of our organs operates as a piece of a much larger system. In a healthy system, the volatile conditions within beta cells are under constant surveillance and regulation by organs that have the tools to manage the oxidative stress that the pancreas cannot — relying on the liver for redox buffering, the gut for barrier integrity, the lymphatics for waste drainage, and the immune system for patrolling toxic debris. These organs work collaboratively to keep beta cells safe in exchange for the energy availability insulin supplies.
Beta cells aren’t weak — they are specialists. But like any specialist, they depend on a coordinated team.
When any of these organs become compromised, there is a systemic strain that alters their ability to provide protection. If the stress becomes chronic and the protective layer buffering the beta cell fails, our insulin-producing friends are woefully unequipped to defend themselves.
🧬 3. The HLA–HFE–HAMP Genetic Cluster: Immunity, Iron, and Islet Fate
The human genome isn’t a fixed script — it’s a dynamic interpreter of the environment. And nowhere is this interplay more significant than in the tight intersection between iron regulation, immune discernment, and metabolic resilience. At the heart of this crossroad lies a cluster of genes that quietly script the terrain of inflammatory disease, diabetes included.
On chromosome 6, within the major histocompatibility complex (MHC), lies a constellation of genes with outsized influence in autoimmunity and iron regulation:
Gene | Function | Link to Disease |
HFE | Iron sensing & transferrin receptor modulation | Mutations cause hereditary hemochromatosis |
HLA-DQA1 / -DQB1 / -DRB1 | Antigen presentation & immune education | Strongest genetic risk for T1D, celiac, MS, RA |
HLA stands for Human Leukocyte Antigen. It is a complex often tied to immune discernment. IE. Recognizing friend versus foe in immune activation. That's the basis for the autoimmunity argument for T1D development. HLA-DQA1 / -DQB1 / -DRB1 are the most common genes used as a predictive tool for T1D development because of their affiliation with autoantibody presentation. For example, HLA-DR4-DQ8 is associated with IAA (insulin autoantibodies) and HLA-DR3-DQ2 is associated with GAD (glutamic acid decarboxylase) (8).
But HLA also encodes iron regulatory genes like HFE. HFE is the gene associated with hereditary hemochromatosis. Both HLA and HFE have an intimate relationship with the HAMP gene (chromosome 19), which encodes for hepcidin expression. I thought it interesting that the immune discernment and iron-regulation stood so close to one another in our genetic code.
Together, these three forces (HFE, HAMP, HLA) form a regulatory triad that dictates:
How much iron is retained
Where it is stored or trafficked
And how the immune system reacts to altered or damaged tissue
When dysregulated, this triad can create a terrain where chronic inflammation, immune misfiring, and metabolic instability become the norm — even in the absence of pathogens.
So why does this matter?
The co-localization of iron-regulating and immune-educating genes suggests that terrain-wide iron imbalance may be a trigger or amplifier of autoimmune signaling.
Individuals with HFE polymorphisms or low hepcidin expression may accumulate more iron in islets, increasing ROS and cellular misfolding—hallmarks of immune system alert signals.
In this model, autoimmunity doesn’t cause diabetes—progressive, subclinical iron overload may create conditions that the immune system interprets as dangerous.
🧬 Genetic Determinism… or Epigenetic Response?
It’s tempting to view diabetes or autoimmunity as genetically predetermined. And in certain cases — such as two copies of C282Y in hemochromatosis — the likelihood of iron overload is high. But that’s not the full story.
There are many people with these mutations who never develop symptoms, just as there are many without them who go on to develop secondary iron overload syndromes, insulin resistance, and chronic inflammation.
This suggests that genetic predisposition is only half of the equation.
The other half?
🌍 Environment. Diet. Mineral balance. Inflammation. Or put more simply: terrain.
A person without any known iron-retention mutations can still suffer from iron overload when exposed to:
Highly fortified foods (breakfast cereals, breads, baby formula)
Chronic alcohol use or gut permeability (leading to excess absorption)
Low intakes of copper, retinol, or ceruloplasmin (iron balancers)
Elevated emotional or metabolic stress (which lowers hepcidin inappropriately)
This is the silent burden of progressive secondary iron overload — a condition that unfolds not through abrupt mutation, but through the slow erosion of system checks and balances.
You can read into this several ways. From a genetic determinism standpoint, the location of the genes themselves symbolizes some intertwined relationship. From an epigenetic, cellular environment standpoint, if the cellular conditions are influencing genetic expression in a certain direction, the likelihood of both iron regulation and immune discernment being affected are much higher. Not to mention the inseparable biological significance of iron in immune function and the influence natural immunity has on iron status.
People may wonder if this is another "chicken or the egg" scenario:
The genes were active ➡️ An imbalance resulted ➡️ The disease progressed
~OR~
An imbalance formed ➡️ The genes were activated ➡️ The disease progressed
The former would lend itself to targeting genetic expression primarily. The latter would focus on identifying and addressing the existing imbalances.
Could we even go so far as to say BOTH could be possible at the same time? Yes, I think so.
Might someone born with gene expression tending towards iron hoarding meet the same fate as someone without the genes but living an iron-dense lifestyle?
Could “genetic risk” actually be terrain-based gene expression, driven by mineral mismanagement?
When you consider the progressive model of iron accumulation introduced by Dr. John Sheldon (explained in Part 3 as well), there is reason to believe that there are factors both internal and external, genetic and environmental, that can coalesce into a disease state.
Consider someone with a genetic predisposition to iron retention. Mutations in the HFE gene cluster like C282Y and H63D are now widely recognized and often labeled by their regional nicknames: “The Celtic Curse,” “Viking’s Disease,” and other ancestral designations tied to Northern European populations. These populations, once vulnerable to iron-deficient environments, evolved to hold onto iron with tenacity. In modern food systems, however, that same tenacity has become a liability. Iron-enriched and fortified foods, pro-inflammatory ingredients and soils depleted of the meaningful vitamin and mineral counterbalances. Is it any coincidence that countries like Finland, Sweden and Norway have some of the highest rates of T1D?
Of note: I just so happen to have Scandinavian and Irish bloodlines.
Even those without the "hardwired" iron insensitivity, think about the generational impacts of iron-overconsumption and its progressive wearing-down of our body's natural balance. The environment could shape iron metabolism—through diet, alcohol, toxins, infections, and stress. Each generation handing down dietary and lifestyle habits that exacerbate the inherited imbalances of each ensuing generation.
Given the progressive onset of iron's damage and the seemingly endless territory that it can impact, conditions both acute and systemic could occur before anemia or overt symptoms.
🔄 Adaptive Systems, Maladaptive Consequences
What if — rather than being a mistake — this iron retention is an adaptive response to past scarcity? And what if the current symptomatology is not genetic failure, but the mismatch between past adaptations and present conditions?
The same genes that once protected us from anemia in iron-poor landscapes may now be overperforming in a world of iron-rich foods and inflammatory stimuli.
And if that’s true, the “cause” of diabetes and related conditions isn’t simply locked in our DNA. It’s in our context — and our context is changeable.
🔄 4. Iron-Induced Insulin Resistance & Glycation
When signaling breaks before secretion
The insulin cascade is one of the most elegant — and delicate — feedback systems in the human body. It begins with glucose entering the bloodstream, prompting the release of insulin from pancreatic beta cells, and ends with glucose being absorbed into cells for use or storage. Along the way, a host of checkpoints regulate the process:
Insulin secretion from beta cells
Insulin binding to receptors
Receptor phosphorylation and signal transduction
GLUT4 transporters facilitating glucose entry
Mitochondrial processing of glucose-derived ATP
Each one of these steps is vulnerable to oxidative stress, and iron accelerates that vulnerability.
Beta cells and their insulin production may be getting the spotlight because of the immediate feedback they provide, but iron doesn’t just damage beta cells—it actively undermines the entire insulin signaling cascade:
ROS (especially hydroxyl radicals) drive non-enzymatic glycation of insulin receptor substrates (IRS), rendering them dysfunctional.
This limits receptor internalization and signaling, even when insulin is present.
The result: functional insulin resistance, despite adequate or even elevated insulin levels.
🔥 The Hydroxyl Radical: A Wrecking Ball, Not a Scalpel
Of all reactive oxygen species (ROS), the hydroxyl radical (•OH) — born from the Fenton Reaction between unbound iron and hydrogen peroxide — is by far the most volatile and indiscriminate.
Unlike other ROS that act as signaling molecules or microbial defenses, hydroxyl radicals damage anything they contact:
Proteins (including insulin receptors)
Phospholipid membranes (compromising cell integrity)
Mitochondrial DNA (disrupting energy production)
Enzymes and kinases critical for glucose handling
In the context of insulin signaling, hydroxyl radicals can:
Glycate receptor proteins, reducing their sensitivity to insulin
Disrupt phosphorylation cascades, preventing downstream effects like GLUT4 translocation
Alter redox-sensitive transcription factors like IRS-1 and PI3K, diminishing insulin’s ability to carry out its job
🧠 In essence, iron overload doesn’t just cause blood sugar to rise — it corrupts the communication system meant to respond to that rise.
Iron accumulation in the liver, muscle, or adipose tissue therefore:
Fuels insulin resistance
Increases glucose exposure to beta cells
Accelerates their overuse, exhaustion, and eventual failure
The insulin-iron web continues to grow. Not only is iron at the root of insulin deprivation at its source, it's also compromising the body's ability to use it. This lends to the clinical observations of phlebotomy being a meaningful way to treat T2D.
⚖️ T1D vs. T2D: A Matter of Which Lever Breaks First?
With iron burning the insulin signaling candle from both ends, might the difference between T1D and T2D be which end gives out first?
This raises a compelling hypothesis:
The difference between Type 1 and Type 2 diabetes lies in which part of the insulin system fails first.
In Type 2 diabetes, the initial dysfunction often lies in the insulin receptor or downstream signaling pathways, leading to insulin resistance. The beta cells continue to produce insulin — even overproduce it — in an effort to compensate.
In Type 1 diabetes, the beta cells themselves become the site of failure — either through immune-mediated destruction, ferroptosis, or chronic oxidative burden — resulting in insulin deficiency despite adequate receptor presence.
But both conditions may share a common terrain:🩸 Iron-rich, inflammatory, redox-imbalanced environments where the weakest link in the insulin circuit gives way first.
This means:
A receptor-dominant vulnerability may manifest as T2D
A beta-cell-dominant vulnerability may manifest as T1D
Both may progress along a continuum of redox and mineral imbalance, where oxidative stress drives deeper compensation — until collapse occurs
The irony of iron: it both disables the key and breaks the lock.
🍬 Glycation: The Sweet Burn
Another iron-fueled pathology relevant here is glycation — the non-enzymatic bonding of sugars to proteins, fats, and DNA. Advanced glycation end-products (AGEs) are:
Elevated in both T1D and T2D
Accelerated by oxidative stress
Linked to retinopathy, nephropathy, and neuropathy
Iron catalyzes glycation reactions through oxidative intermediates, making the very presence of unbuffered iron a fuel source for diabetic complications, even before insulin dysfunction becomes overt.
⚰️ 5. Ferroptosis: The Final Blow
If oxidative stress is the fire, ferroptosis is the point at which the house collapses.
Unlike other forms of cell death (like apoptosis or necrosis), ferroptosis is iron-dependent and uniquely tied to the collapse of cellular membranes due to lipid peroxidation. In beta cells, this isn’t just a failure of one antioxidant pathway — it’s the final consequence of a full-system breakdown.
🧫 What Is Ferroptosis?
Ferroptosis is a regulated form of cell death triggered by:
Uncontained iron (especially Fe²⁺)
Lipid-rich membranes vulnerable to oxidation
Insufficient antioxidant defense, especially glutathione and GPX4
Impaired mitophagy and autophagy
When iron catalyzes lipid peroxidation and the cell can’t neutralize it, the cell membrane ruptures. This is not a clean shutdown — it’s a messy, inflammatory collapse that releases danger signals to neighboring cells and immune responders.
🔁 Mitochondrial Breakdown: The Spark Inside
Beta cells are mitochondrial powerhouses, but that comes with a cost:
High ATP demand = High ROS production
Low antioxidant reserves = Low cleanup capacity
Rich phospholipid membranes = Perfect fuel for lipid peroxidation
Mitochondria under stress should be recycled via mitophagy — a process where damaged mitochondria are tagged and broken down before they can leak ROS. But when overwhelmed, this system fails.
Result: mitochondrial ROS spillover, iron accumulation, and lipid-rich mitochondrial membranes become a bomb primed for ferroptosis.
🧹 Autophagy Breakdown: When Recycling Stalls
Autophagy is the cell’s waste-management system — breaking down damaged proteins, misfolded enzymes, and organelles. It also helps recycle antioxidant precursors, iron-handling proteins, and membrane lipids.
But in states of:
Liver dysfunction (decreased iron recycling, elevated ferritin)
➡️ The liver is iron-laden, vitamin and mineral deficient and unable to keep up with the needs of an increasingly inflamed body.
Gut permeability (endotoxin overload, chronic inflammation)
➡️ The gut is unable to sustain a healthy microbial balance or the necessary GI barrier integrity. Deficient in the necessary nutrients, fibers and probiotic life.
Nutrient deficiency (low sulfur, selenium, PUFAs, choline, etc.)
➡️ Food goes undigested, vitamins and minerals absent, pathogens thrive and the body is left undernourished and unable to sustain the defenses and repairs necessary to self-correct.
Autophagy stalls. Instead of recycling the components necessary to prevent ferroptosis, the cell becomes a storage unit of unresolved chaos.
🧱 Membrane Integrity: The Final Frontier
Cellular membranes aren’t just walls — they are intelligent lipid bilayers embedded with receptors, channels, and identity markers. In beta cells, their integrity determines:
Insulin release
Glucose sensing
Immune visibility
Inflammatory containment
Once the membrane is breached via lipid peroxidation, there’s no coming back. The beta cell spills its contents, inviting immune attack and amplifying the cycle of inflammation.
⚙️ Systemic Failures that Precipitate Ferroptosis
Ferroptosis in beta cells doesn’t arise in a vacuum. It’s the final step in a terrain-wide collapse, with contributions from:
System | Breakdown | Contribution to Ferroptosis |
Liver | Poor iron recycling (↓ferroportin, ↓ceruloplasmin) | Iron retention, GPX4 depletion |
Gut | Permeable lining, dysbiosis | LPS/endotoxin exposure, inflammatory cytokines |
Diet | Iron-fortified, processed foods, low antioxidants | No raw materials for membrane repair or antioxidant synthesis |
Adrenals | Chronic stress, high cortisol | Glutamate buildup, impaired glutathione synthesis |
Mitochondria | ROS overload, defective mitophagy | Iron accumulation, redox failure |
Immune system | Constant threat signaling | Inflamed terrain, no room for tolerance |
Endocrine | Low T3, low testosterone | Reduced cell turnover and repair |
The rate and specificity of deterioration with each of these systems differs from person to person. With each new deficit, a new drain isplaced on the systemic balance. There is a period of adaptation and stabilization. But as conditions remain insufficient, the drains become greater, the adaptations shorter lived. Suffer and adapt. Suffer and adapt. Until finally the series of adaptations reaches its breaking point.
Ferroptosis isn’t just death—it’s a collapse in cellular sovereignty, and a signal that the terrain has failed its most precious regulator.
🔚 Conclusion — The Final Straw
We began by uncovering the iron-sensitivity of beta cells, their mitochondrial density, their antioxidant fragility, and their central role in glucose–iron cross-talk. These qualities don’t make them weak — they make them specialized, finely tuned to a terrain that must remain stable.
Next, we explored how genetic susceptibility (HFE mutations, HLA variants, hepcidin regulation) intersects with environmental excess to overload iron pathways. For some, it’s inherited. For others, it’s induced. But the result is the same: iron goes unbuffered and ROS carves chaos into sensitive metabolic terrain.
We then zoomed in on insulin resistance — not as a standalone disease, but as an early signal that redox chemistry and receptor integrity are faltering under stress. When iron transforms the insulin receptor into a dysfunctional switch, the system compensates — until it no longer can.
Finally, we arrived at ferroptosis, the terminal end of unchecked inflammation. A death spiral of mitochondrial breakdown, antioxidant depletion, and lipid membrane collapse. Beta cells don’t fail because they’re defective — they fail because every system meant to support them is already on fire.
🧩 The Emerging Picture
Each of the previous four articles has pointed us toward this central truth:
Iron is essential, but volatile.
Inflammation is intelligent, but context-dependent.
Systemic stability is earned, not assumed.
And the beta cell sits at the convergence point of it all.
When the liver stops recycling, the gut becomes porous, the immune system stops tolerating, the endocrine axes lose coherence, and iron continues to circulate unchallenged…
…the beta cell becomes the final straw.
📚Reading Material:
🔬 Iron Metabolism, Hepcidin, and the Beta Cell
Nemeth, E., & Ganz, T. (2006). Regulation of iron metabolism by hepcidin. Annual Review of Nutrition, 26, 323–342.https://doi.org/10.1146/annurev.nutr.26.061505.111303
Wang, C. Y., & Babitt, J. L. (2019). Hepcidin regulation in the anemia of inflammation. Current Opinion in Hematology, 26(3), 138–145.https://doi.org/10.1097/MOH.0000000000000492
Zhang, C., et al. (2011). Beta cells express hepcidin, an iron-regulatory hormone linked to protection against oxidative stress. Diabetologia, 54(2), 419–426.https://doi.org/10.1007/s00125-010-1970-3
Del Guerra, S., et al. (2005). Iron-induced oxidative stress in isolated human pancreatic islets: a possible role in beta-cell failure. Histochemistry and Cell Biology, 124(5), 435–442.https://doi.org/10.1007/s00418-005-0059-6
🧬 Genetic & Epigenetic Considerations (HFE, HLA, and Autoimmune Crossroads)
Pietrangelo, A. (2004). Hereditary hemochromatosis — a new look at an old disease. New England Journal of Medicine, 350(23), 2383–2397.https://doi.org/10.1056/NEJMra031573
De Groot, A. S., et al. (2008). Genome-wide scan reveals HLA-associated susceptibility to Type 1 diabetes. Diabetes, 57(8), 2176–2183.https://doi.org/10.2337/db07-1734
Anderson, G. J., & Frazer, D. M. (2017). Current understanding of iron homeostasis. The American Journal of Clinical Nutrition, 106(suppl_6), 1559S–1566S.https://doi.org/10.3945/ajcn.117.155812
Robertson CC, Rich SS (2018): Genetics of type 1 diabetes. Curr Opin Genet Dev 50: 7-16.
🔥 Iron-Induced Inflammation, Insulin Resistance & Glycation
Fernández-Real, J. M., & Manco, M. (2014). Effects of iron overload on chronic metabolic diseases. The Lancet Diabetes & Endocrinology, 2(6), 513–526.https://doi.org/10.1016/S2213-8587(14)70034-0
Cooksey, R. C., et al. (2004). Dietary iron restriction or iron chelation protects from diabetes and loss of beta-cell function in the obese (ob/ob lep−/−) mouse. The American Journal of Physiology-Endocrinology and Metabolism, 287(5), E939–E947.https://doi.org/10.1152/ajpendo.00174.2004
Simcox, J. A., & McClain, D. A. (2013). Iron and diabetes risk. Cell Metabolism, 17(3), 329–341.https://doi.org/10.1016/j.cmet.2013.02.007
🧨 Ferroptosis, Mitochondrial Stress, and Beta Cell Failure
Tuo, Q. Z., et al. (2017). Iron, ferroptosis, and ferroptosis-related diseases. Frontiers in Pharmacology, 8, 592.https://doi.org/10.3389/fphar.2017.00592
Arner, E. S. J. (2004). Focus on mammalian thioredoxin reductases—important selenoproteins with versatile functions. Biochimica et Biophysica Acta (BBA) - General Subjects, 1790(6), 495–526.https://doi.org/10.1016/j.bbagen.2009.01.014
Conrad, M., & Pratt, D. A. (2019). The chemical basis of ferroptosis. Nature Chemical Biology, 15, 1137–1147.https://doi.org/10.1038/s41589-019-0362-4
🧠 Historical Perspectives on Iron & Diabetes
Sheldon, J. H. (1935). Haemochromatosis. Oxford University Press.(Classic monograph introducing the concept of primary vs. secondary iron overload and systemic damage)
Trousseau, A. (1865). Clinique Médicale de l’Hôtel-Dieu de Paris. Vol 2.(Documented one of the first links between iron overload, jaundice, and glucosuria — a pivotal early observation on the intersection of liver iron and diabetes)
📘 Further Reading for Enthusiasts & Practitioners
Andrews, N. C. (1999). Disorders of iron metabolism. New England Journal of Medicine, 341(26), 1986–1995.
Kell, D. B., & Pretorius, E. (2014). Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics, 6(4), 748–773.
Torti, F. M., & Torti, S. V. (2013). Iron and cancer: more ore to be mined. Nature Reviews Cancer, 13(5), 342–355.
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