Diabetes and chronic cellular stress

Diabetes, to my surprise, results from chronic cellular stress. The source of the stress is both legion and not really important to understanding what diabetes is. It all begins with the endoplasmic reticulum, an organelle inside every cell in our body.

The Endoplasmic Reticulum

The endoplasmic reticulum (ER) is an organelle in every cell in the body that is responsible for the folding, sorting and transport of proteins. On the surface of the ER are ribosomes that sequence amino acids into peptides and stuff the peptides through holes in the ER. Once inside the ER, chaperone proteins oversee the correct folding of the peptides into proteins, sometimes making small modifications to the peptides in the process.

If a peptide misfolds, the chaperones may help in refolding the protein or they may transport the misfolded protein to a location where it will be torn back down into its basic amino acids.

Physically, the ER looks like a series of boxes and tubes. It has been recently discovered that some of those tubes actually pass through the cell’s nucleus.

ER Stress

ER Stress, a sudden demand for increased protein production, occurs as a response to environmental situations such as wound healing. ER Stress is usually short lived and normal.

The Unfolded Protein Response

On the surface of the ER, sticking out like hairs, are strands of the protein ATF6a. If ER Stress occurs for an extended period of time or is severe, the ER may run low on chaperone proteins and unfolded peptides begin backing up in the ER. This condition is detected by the ER and produces the Unfolded Protein Response (UPR). UPR is simply the cleaving of ATF6a from the surface of the ER. Upon entering the nucleus of the cell, ATF6a causes the nucleus to call for increased production of chaperones; that is, it causes the genes for producing chaperones to be turned on.

I liken this to a factory that has more orders to do the final assembly work on proteins than it can handle. It requests from management more workers to fill the orders. In this case, the factory would also be manufacturing the additional workers, the chaperones.

Chronic ER Stress

When ER Stress occurs for protracted lengths of time, the ER starts running out of ATF6a; that is, the production of new chaperones decreases despite the continued need for them. This results in a cascade of events that result in the cell becoming increasingly insensitive to insulin. This is a protective response.

If you think of the factory analogy, this would be the case where the factory cannot obtain enough workers to keep up with the work load and the factory is filling up with unfinished product (unfolded proteins). The logical response at this point would be to slow down the arrival of peptides needing folding.

Because a cell’s response to insulin is not only the taking in of glucose but also the taking in of amino acids, insulin resistance slows the production by the ribosomes of peptides. That reduces ER Stress, but does not cure it unless the stressor that led to the state is removed. If the stressor is not removed, it will either be a holding action or a war lost.


If the condition of the ER continues to degrade, once again the cell changes response. At this point the cell appears to its own apparatus to be irreparably damaged and orderly cell death (apoptosis) is initiated.

The Cure

Chronic ER Stress can result from innumerable environmental conditions – the internal environment of the body. Excessive glucose, lipids, toxins, chronic infections, and inflammatory cytokines are among the most common environmental conditions that lead to diabetes. Anything that requires the continuous, never-ending need to produce structural or secretory proteins will cause chronic ER Stress. This is why the “cause of diabetes” was so elusive.

To cure diabetes (and many other old age illnesses) it is necessary to reinforce, to actually grow, the ER so that it can handle the stress. At the same time, it is necessary to remove as many stressors as possible.

Short diabetes story of an anonymous person

At the beginning of this journey, I was obese, had high fasting blood sugar, high blood pressure, a high resting heart rate and very low energy. I began my exercise program. Not because I thought that was a good idea, but because I couldn’t do any more.

Over the first two years, my fasting blood glucose level slowly and linearly dropped 35 points along with a 45 pound slow drop in my weight. After another year my fasting glucose level had fallen another 20 points and my weight another 20 pounds. Then I bought a far-infrared sauna. A temperature above 42 degrees Celsius for 30 minutes will activate HSF-1 (and burn 200 calories). I also learned I was low in testosterone and began supplementation with bio-identical testosterone. The result was that after three months my fasting glucose suddenly dropped to the low 80s and I was out of the diabetes woods – I considered myself cured. Other symptoms of diabetes are slowly disappearing. My father and grandfather both had and died of diabetes, both at about my age – one younger, one older. There is no doubt in my mind that diabetes is accelerated aging. In every way, the clock has reversed for me. Jack LaLane was the first to recommend aerobic exercise and weight training for seniors. He has said that exercise and clean eating are the key to a long healthy life and at 95, he and his wife were living proof of that claim.

Now, here is something to think about. Chronic ER Stress can occur in any organ or in many at the same time. Depending on which organs are affected, different symptoms will appear. Diseases are a collection of symptoms, so chronic ER Stress can lead to many seemingly different diseases. But all might be manifestations of the same disease process.

Like many diabetics, I also had cardio-vascular disease (CVD). My blood pressure taken via my right arm was 15 points lower than my blood pressure taken with my left arm. During the five years described above, my blood pressure went from 185/120 with resting heart rate of 109 to 106/68 with a resting heart rate of 67, and my blood pressure is now the same for both arms. It was actually my third collapse from heart problems that got me started on this road.

Why does it take a near-death experience to get people moving? I don’t know, but I was lucky that it was only “near”.

I do believe, based on the number of stated causes for CVD that it, too, results from chronic ER stress from multiple sources such as inflammatory cytokines, oxidized fats, viral and bacterial infections, environmental toxins and much more. Energy is necessary to heal the body and to make it function properly. It doesn’t matter what function you are talking about, they all require energy and optimizing energy production is key in any recovery and to living a long, healthy life. The more energy you have, the bigger the insult to the body you can survive. Eating right, keeping your body in balance and exercising hard are together the key to keeping your energy levels high.

I don’t know who said it, but “Death is when you stop moving”. It sounds like something Jack LaLane probably said or wished he had.

Lipoic Acid for Diabetic Neuropathy

Lipoic acid, also called alpha-lipoic acid, is a natural treatment for diabetic neuropathy. Lipoic acid is a remarkable antioxidant that can work together with antioxidants such as vitamins C and E in the body to protect tissues from damage by free radicals (oxidative stress).


Researchers have studied the effects of lipoic acid for extended periods of time and found that a total daily dose of 600 mg per day markedly lessened the chronic pain from nerve damage that many diabetics experience as a complication of their condition. One study even found that when diabetics whose neuropathy pain was relieved with lipoic acid were switched over to one or more common conventional drugs for the pain problem (such as gabapentin or Neurotonin), the pain returned within 2 weeks in 3/4 of the diabetics.

In other words, alpha-lipoic acid is an effective treatment for pain relief from chronic diabetic neuropathy, and it appears better than mainstream pain medications in its effects. The side effects and costs of lipoic acid are also lower than with drugs.

Diabetics who want to try lipoic acid should be aware that one of its most common side effects is nausea and sometimes vomiting. A way to deal with that is to start with a much lower dose, divided during the day and taken with food.

Some people find that dispersing the lipoic acid in a nutrient-rich drink of protein powder and low glycemic fruits will also reduce the nausea side effect. The idea is to keep the capsules from dissolving all at once in one place in the stomach, especially since many diabetics also have slowed emptying of the stomach. Foods and supplements may stay in the stomach much longer than in a non-diabetic person.

Lowering of blood sugar levels

An additional major benefit of lipoic acid is that it can lower blood sugar in diabetics, thus reducing the requirements for insulin and oral hypoglycemic drugs as well. This lowering of blood sugar naturally from the antioxidant’s effects can be quite strong — so, as with any natural supplement, anyone taking a drug to lower blood sugar should monitor their blood sugar closely and work with their doctor to lower their medications gradually as needed.

In summary, lipoic acid for diabetic neuropathy works well. The long term benefits of this natural treatment for diabetes go beyond those of drugs, and the the costs and side effects are lower. The “R” form of lipoic acid is the best, as it is the most biologically active. If you are a diabetic with peripheral neuropathy or nerve pain, lipoic acid may be a nutritional strategy to help you live a more normal and comfortable life with diabetes.