In book and previous blog posts I discuss genotype and phenotype.  So, some new exciting research has come out today as I am writing this. Where as in the past they tried to blame cholesterol and calcium as cause of atherosclerosis, it is not. By explaining how exercise works will help explain atherosclerosis.

Exercise is important as it speeds the blood flow in our arteries. Recent research has shown faster blood flow triggers an enzyme called extracellular signal-related kinase 5 (ERK-5). ERK-5 signals the endothelial nitric oxide synthase (eNOS). 1 eNOS then produces more NO.

To digress I wonder if it is the speed of the blood or it is the increased pulse wave causing stretching of the artery, increasing its diameter that activates this gene. It does not state, nor could I find if they in this study took this into account. 2 However the body does have nerves that detect stretching but none I am aware of that measure speed.

Back to NO. It causes arteries to dilate allowing more blood and oxygen to flow to the area. When we exercise this is how our body knows where to send more blood and oxygen to “feed” the muscles and other tissues requiring oxygen and nutrients in the blood. 3 Also to remove waste products and CO2.

ERK-5 also activates two factors that block the immune system from finding damaged blood vessels. They are Kruppel-like factor 2 (KLF2) and peroxidase proliferator-activated receptor-g (PPARg). 4 Why is this important? It prevents the healing process from depositing cholesterol and calcium.

Thus, preventing the stiffening and narrowing of the arteries. This preventing peripheral artery disease (PAD). Circuitous and perhaps more then you wanted or needed to know. Like I say to fully understand something you need to get to the basics. I don’t always dig down to the itty bitty stuff, but I do try to explain enough that can support my opinion.

This same research is the first to show how diabetes (both type I and II, as both have elevated blood sugar in common) interferes with this process. How diabetes prevents fast blood flow from protecting blood vessels by interfering with ERK5 and it is signaling partners. 5

They discuss models for peripheral artery disease (PAD) that occurs with decreased blood flow. 6 Well obesity is the key to type II diabetes. It is self-fulfilling in a sense. As insulin signals to the brain that there is plenty of “energy”. That is at increased insulin levels it signals satiety, no need to eat more. 7

Well if the cells are resistant to insulin like in type II diabetes this doesn’t happen. The brain insulin receptors that signal satiety also are resistant. 8 Leptin is also block. It helps control the uptake of fat by cells and signals to brain satiety.

Well as I explained before vitamin D3 causes the release of leptin release in keratocytes which are cells that make up skin. Either through exposure to ultraviolet light like in sunshine or the ingestion of vitamin D. Thus, helping to stimulate satiety.

However, in those who are resistant to both leptin and insulin probably will not respond or will have a smaller response. This makes sense to me now why I saw such large weight losses in non-diabetics but not in those who were diabetic.

Leptin is also released by the small intestine, here is the gut again, so with vitamin D3 effect on gut health it may help here too. So overeating causes chronic inflammation causing type II diabetes which causes diminished immune function which causes the gut to suffer.

A damaged gut then allows more toxic substances to leak into our blood stream and can’t prevent harmful fungi, bacteria or other organisms from multiplying.  Vitamin D3 in these cases will take longer to help. As it boosts the immune system it can help restore the gut and block this absorption.

Reducing the influx of inflammatory substances. Vitamin D3 by boosting the immune system restores the balance by increasing the growth of helpful and decrease growth of harmful organisms. This is a start as the goal is to reduce inflammation so that the cells again will respond to insulin and leptin. More in next post.

  1. University of Rochester Medical Center. (2008, March 17). How Diabetes Drives Atherosclerosis. ScienceDaily. Retrieved April 16, 2019 from
  2. Ibid.
  3. Ibid.
  4. Ibid.
  5. Ibid.
  6. Morris A, Brewster LP, Timmins L. (October 2017) Developing models of disturbed flow in infrageniculate arteries. J Am Coll Surg. 225;(4):sup. 1, S216.
  7. Woods SC, Seeley RJ. (2000 Adiposity signals and the control of energy homeostasis. Nutrition 16:894-902.
  8. Sandoval DA, Obici S, Seeley RJ. (2009) Targeting the CNS to treat type 2 diabetes. Nat Rev Drug Discov. 8:386-398.

*The information posted above is for educational purposes only. Always check with your doctor before initiating any changes in your medical treatment. If you do not, then The Two-Minute Health Fact, Dr. Judson Somerville, nor The Optimal Dose is responsible!

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