When most people think about calcium, they often associate it with bone health and strong teeth. However, calcium plays a much broader role in the body, particularly in the regulation of blood sugar levels. This essential mineral is a key player in the release of insulin, the hormone responsible for lowering blood glucose levels. In a healthy body, calcium ions facilitate the proper function of insulin-secreting cells in the pancreas, ensuring that blood sugar remains within a safe range.
However, in individuals with diabetes, the balance and function of calcium can become disrupted, leading to complications in insulin release and glucose metabolism. Understanding how calcium is altered in those with diabetes is critical for managing the condition effectively and could provide new insights into potential therapeutic approaches.
In this article, we'll explore the vital connection between calcium and insulin, how this relationship is impacted by diabetes, and what it means for those striving to manage or even reverse this chronic condition.
If you'll remember from a previous article on the cellular pathway of insulin release, calcium plays a pivotal role in getting insulin into the bloodstream. In healthy beta cells, glucose metabolism leads to an increase in the ATP/ADP ratio, which closes ATP-sensitive potassium channels and depolarizes the cell membrane. This depolarization opens voltage-dependent calcium channels, allowing calcium ions to enter the cell. Elevated intracellular calcium triggers the exocytosis of insulin granules.
For those with T1D, this calcium balance is disrupted and insulin is no longer properly released.
The $1 billion questions now become:
"What is disrupting the calcium influx required to release insulin?"
"Does calcium have additional roles elsewhere in the body that impact insulin production/release?"
"How can we effectively integrate proper calcium dynamics into treatment plans?"
These questions requires us to peel a few layers back on exactly how type 1 diabetes develops. Seeing as there are multiple theories on the root causes of T1D involving multiple body systems, pathogens and lifestyle factors, we need to cover our bases. And don't forget a complex web of mineral interactions impacting the role and function of each nutrient and constant cellular feedback loops fighting for stability in an inherently unstable state. The task looms large.
So we know calcium's role in insulin release. Is it impacting any other facets of beta cell function?
Look no further than the endoplasmic reticulum (ER) of beta cells. The ER is a cellular organelle involved in protein folding, modification, and transport. Under normal conditions, the ER ensures that proteins are correctly folded before they are sent to their destination. However, when cells face conditions that overwhelm the ER's capacity to correctly fold proteins, misfolded or unfolded proteins accumulate, causing ER stress. This stress can lead to cell dysfunction and even death if it’s not adequately managed.
Calcium ions play a critical role in the functioning of the ER, especially in protein folding. The ER stores high concentrations of calcium, which are essential for the activity of various chaperone proteins involved in the protein-folding process. When there’s a disturbance in calcium homeostasis, it can exacerbate ER stress.
Beta cells, because of their high metabolic activity, are creating and folding more proteins than a typical cell and thus have an atypically large ER.
So take a second to consider all this: 1. The ER is where proteins are assembled, folded and packaged for the body.
2. Calcium is a major player in the proper function of the ER.
Therefore, the ER needs a lot of calcium.
1. Beta cells make a lot of proteins (insulin).
2. The ER of beta cells is larger than normal and thus stores more calcium.
Therefore, any disruption of calcium signaling is not only effecting insulin release but also insulin production.
Now let's take a closer look at how our inflammatory processes and immune regulation play into calcium homeostasis.
To get the most out of addressing inflammation, let's cover the two main categories that we're interested in.
The initial stimuli
This is ground zero. The source (or sources) that is causing our body to recognize a threat to our well-being.
2. The cascade
This is the resulting feedback loop that follows the initial stimuli. These are the elements of our immunity that are called into action once the initial stimuli requires additional resources. Its a self-regulating function of sizing up inflammation, enacting our immune system to the correct degree, and stopping once the threat has been addressed. This cascade, when improperly regulated, is the basis for "autoimmunity".
Why this matters when looking at calcium in beta cells is because those with T1D have several facets of their immunity chewing away at their calcium dynamics. We all have a pre-existing degree of inflammation independent of autoimmunity. Combine that with an out of control immune-regulating feature exhausting our nutrient resources. There is a source of stress before calcium signaling goes haywire.
Much of the current medical narrative begins at the autoimmune phase. But consider that the incessant "autoimmune" attack is a cycle that is triggered. And also consider how long this autoimmunity exists before becoming clinically significant. Might our diagnoses be at the crescendo of a years long build up of inflammation and compensations?
Focusing on restoring calcium levels resulting from the cascade, as opposed to the initial stimuli, is merely symptom management. In healing there is a component of breaking the immunity cycle, as well as identifying and targeting the trigger.
When I think about what aspect of inflammation to "blame", I see the time of exposure as the primary issue. Long-term exposure to low to mid-grade inflammation is (in my opinion) the primary culprit in disrupting calcium balance. The inflammation may be long-term exposure to a trigger or an unchecked autoimmune loop. Any form of oxidative stress, if endured long enough, can alter calcium signaling. Our body is incredibly adaptable in the short term to restore balance. But with hyper-stimulated defenses and exhausted natural resources, a chronically inflamed body loses its ability to adapt.
Some possibilities for sources of long-term inflammation involve food, life stress and lifestyle choices. My main focus in restoring beta cell function has been nutrient balancing. I reason that every cell has an ideal balance of vitamins and minerals that serves to equip its function and ability to adapt. When I saw the cell's function described in terms of elements like magnesium, calcium and sodium, it made sense that food would be an ideal starting place.
From a food perspective, our diet's primary purpose is to supply our body with the nutrients required by each cell for them to do their job. Each cell has its own list of must-haves in specific ratios and sequences. Ion channels, neurotransmitters, cell membranes and T cells all owe their existence to the carbohydrates, fatty acids and amino acids we consume on a daily basis.
So if our diet lacks any number of the necessary nutrients our cells need do their job, or neglects the ratio and diversity required to build effectively, the cell's function suffers. I argue that in the modern world dominated by processed and artificially enriched foods, our collective nutritional status from generation to generation has deteriorated to a point of extreme dysfunction.
Our lifestyles are dominated by hyper-sympathetic states of being (worrying, processing trauma, anxious and depressed). When in doubt, stress it out. But these chronic stressors exhaust a nervous system using vitamins and minerals as its energetic currency. Magnesium is king here. Magnesium burn rate (MBR) is a baseline measure of how quickly our body uses and depletes magnesium. Stress and illness are known for increasing MBR.
Don't forget to visit my Thorne Research storefront. I give a comprehensive list of supplements I use, including everything mentioned in this article, to improve my health.
Magnesium is a natural calcium channel blocker. It helps regulate the flow of calcium into cells. When magnesium levels are low, calcium channels may remain open longer, leading to an increased influx of calcium into cells. This excessive intracellular calcium can disrupt normal cellular functions.
With poor nutrient availability and our body's control panel wired to further exhaust our existing stores, the body's natural immunity reads each of the cries of our cells as a sign to act. This can trigger the release of inflammation markers and cytokines.
ER stress can be exacerbated due to inflammatory cytokines and the autoimmune attack on beta cells, leading to disruptions in calcium homeostasis. Disrupted calcium homeostasis can further exacerbate ER stress, creating a vicious cycle that contributes to beta cell dysfunction and death.
The autoimmune attack associated with T1D involves the release of various inflammatory cytokines (like interleukin-1β, TNF-α, and interferon-γ). These cytokines can disrupt calcium signaling by affecting calcium channels and pumps in beta cells. This disruption further compromises the cell's ability to regulate calcium levels effectively, impairing insulin secretion and contributing to beta cell apoptosis.
Now armed with insight into why we're lacking the proper nutrients and how that manifests in our body's immune function, let's consider how we can make meaningful changes.
There are homeopathic and allopathic means of targeting calcium.There is potential in both and I speculate that both can work together to bring about important discoveries.
Homeopathically, mending our calcium balance is a game of taking away what skews the balance and putting in what restores it. This differs from person to person. Magnesium, Vitamin D, Boron, Vitamin and Zinc are all tools our bodies use to ensure calcium is being absorbed and utilized properly. Remember that with the skewed balances of a standard western diet, we're likely not dealing with outright calcium deficiency but a shortage of calcium adjuncts.
Avoid excess sugar, enriched grains and PUFAs to decrease the inflammatory effects of your food. Eliminate processed foods, sugary drinks and commit to learning how to cook with whole foods.
In our day to day lives, seek ways to regulate your nervous system. Time outside in nature, breathwork and designated periods of deliberate relaxation are good practices in restoring a hampered parasympathetic nervous system. Herbs like lemon balm, valerian root and passion flower all help to restore a sense of relaxation.
Allopathically, the calcium dynamics of insulin release are becoming a topic of interest in type 1 diabetes research. There has been some initial success preserving beta cell mass using calcium channel blockers.
The prescription Ca++ channel blocker verapamil has been the subject of several scientific studies exploring the role of ion channel regulation in beta cell preservation (1,2,3,4).
Verapamil helps reduce ER stress in the following ways:
Stabilizing Calcium Levels:
Verapamil blocks L-type calcium channels, which can help regulate and stabilize intracellular calcium levels. By preventing excessive calcium influx into the cell, verapamil helps maintain a balance that is crucial for proper ER function and reduces the likelihood of inducing ER stress.
Reducing Inflammatory Signaling:
Inflammation often accompanies ER stress. Verapamil has anti-inflammatory properties that can reduce inflammation in beta cells. By mitigating inflammatory responses, verapamil indirectly contributes to reducing the burden on the ER.
Improving Cellular Homeostasis:
By improving calcium homeostasis, verapamil helps ensure the ER has the appropriate environment to perform its functions efficiently. This can improve the overall health of beta cells and enhance their ability to produce and secrete insulin effectively.
There are also indirect ways of influencing calcium. Leveraging calcium's relationship with other minerals and ion channels (like potassium) has potential as well. Remember that in the release of insulin, potassium ion channels close and depolarize beta cell membranes. This depolarization causes the influx of calcium that signals insulin release.
4-aminopyridine (4-AP) is a potassium channel blocker. For those with T1D, especially those newly diagnosed having more residual beta cells remaining, a potassium channel blocker can stimulate that initial depolarization of the beta cell membrane to initiate the calcium influx leading to insulin release. I have heard anecdotal stories from followers of mine having had success using 4-AP to stabilize blood sugars and decrease insulin usage.
Calcium’s role in the body extends far beyond its well-known function in bone health; it is a critical player in the intricate process of insulin release and blood glucose regulation. In healthy individuals, calcium facilitates the efficient functioning of pancreatic beta cells, ensuring that insulin is released in response to rising blood sugar levels. However, in those with diabetes, the delicate balance of calcium is often disrupted, leading to impaired insulin secretion and further complicating glucose management.
Understanding how calcium is altered in diabetes provides valuable insights into potential therapeutic strategies. By focusing on maintaining optimal calcium levels and supporting nutrients that aid in calcium metabolism, individuals with diabetes may find new avenues to improve their condition. Whether through diet, supplementation, or lifestyle changes, restoring calcium balance could play a crucial role in better managing diabetes and enhancing overall health.
As research continues to uncover the complexities of calcium’s role in diabetes, it becomes increasingly clear that addressing these alterations is not just about managing symptoms but also about tackling the underlying mechanisms of the disease. By integrating this knowledge into diabetic care, we can take meaningful steps towards more effective treatments and, ultimately, better outcomes for those living with diabetes.
CITATIONS AND REFERENCES
1. Title: "Verapamil preserves β-cell function in overweight adults with recent-onset type 1 diabetes"
Authors: John E. Hall, Christine M. Wright, Debra A. Bryant-Greenwood, et al.
Journal: Nature Medicine
Published Year: 2018
Summary: This study investigated the effect of verapamil on preserving beta cell function in overweight adults with recent-onset T1D. The randomized, double-blind, placebo-controlled trial showed that verapamil preserved insulin secretion and slowed the decline of beta cell function.
2. Title: "Verapamil and beta-cell function in adults with recent-onset type 1 diabetes"
Authors: Paolo Fiorina, Francesco Stellarini, Jacinta Lara Fabis-Pedrini, et al.
Journal: Diabetes Care
Published Year: 2019
Summary: This paper focused on the mechanisms by which verapamil could preserve beta-cell function in adults with recent-onset T1D. It detailed the cellular processes affected by verapamil, including ER stress reduction and inflammatory cytokine suppression.
3. Title: "Calcium Channel Blockers as Potential β-Cell Protectors in Type 1 Diabetes"
Authors: Anath Shalev, Philipp F. Bosch, Mordechai D. Resnick, et al.
Journal: The Journal of Clinical Investigation
Published Year: 2017
Summary: This study explored the role of calcium channel blockers, like verapamil, in protecting beta cells from apoptotic cell death in T1D. The findings highlighted verapamil’s potential in reducing ER stress and preserving beta-cell function.
4.Title: "Verapamil and beta cell function in adults with recent-onset type 1 diabetes."
Authors: Ovalle, Fernando & Grimes, Tiffany & Xu, Guanlan & Patel, Anish & Grayson, Truman & Thielen, Lance & Li, Peng & Shalev, Anath.
Journal: Nature Medicine.
Published Year: 2018
Summary: Investigates the potential of Verapamil, a calcium channel blocker, to preserve beta cell function and improve endogenous insulin production in adults recently diagnosed with Type 1 Diabetes, showing promising results that suggest Verapamil may help mitigate beta cell decline and enhance metabolic control in this patient group.
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