A Natural Protein to Control High Blood Pressure and Diabetes

 A Protein Expressed by Our Body that may be able to Control High Blood Pressure and Diabetes?

Here’s an article below I received on 21 February, 2022 from a friend of mine Professor Dr Andrew Charles Gomez who is a Senior Head and Neck Surgeon through our Whatsapp Chat group.

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Long-Standing Enigma Finally Cracked – Link Discovered Between High Blood Pressure and Diabetes

 

 By UNIVERSITY OF BRISTOL FEBRUARY 21, 2022

 

The long-standing enigma of why so many patients suffering with high blood pressure (known as hypertension) also have diabetes (high blood sugar) has finally been cracked by an international team led by the universities of Bristol, UK, and Auckland, New Zealand. 

The important new discovery has shown that a small protein cell glucagon-like peptide-1 (GLP-1) couples the body’s control of blood sugar and blood pressure.

Professor Julian Paton, a senior author, and Director of Manaaki Manawa – The Centre for Heart Research at the University of Auckland, said: “We’ve known for a long time that hypertension and diabetes are inextricably linked and have finally discovered the reason, which will now inform new treatment strategies.”

The research, published online ahead of print in Circulation Research on February 1, 2022, involved contributions from collaborating scientists in Brazil, Germany, Lithuania, and Serbia, as well as the UK and New Zealand.

GLP-1 is released from the wall of the gut after eating and acts to stimulate insulin from the pancreas to control blood sugar levels. This was known but what has now been unearthed is that GLP-1 also stimulates a small sensory organ called the carotid body located in the neck.

The University of Bristol group used an unbiased, high-throughput genomics technique called RNA sequencing to read all the messages of the expressed genes in the carotid body in rats with and without high blood pressure. This led to the finding that the receptor that senses GLP-1 is located in the carotid body, but less so in hypertensive rats.

David Murphy, Professor of Experimental Medicine from Bristol Medical School: Translational Health Sciences (THS) and senior author, explained: “Locating the link required genetic profiling and multiple steps of validation.  We never expected to see GLP-1 come up on the radar, so this is very exciting and opens many new opportunities.”

Professor Paton added: “The carotid body is the convergent point where GLP-1 acts to control both blood sugar and blood pressure simultaneously; this is coordinated by the nervous system which is instructed by the carotid body.”

People with hypertension and/or diabetes are at high risk of life-threatening cardiovascular disease.  Even when receiving medication, a large number of patients will remain at high risk. This is because most medications only treat symptoms and not causes of high blood pressure and high sugar.

Professor Rod Jackson, world-renowned epidemiologist from the University of Auckland, said “We’ve known that blood pressure is notoriously difficult to control in patients with high blood sugar, so these findings are really important because by giving GLP-1 we might be able to reduce both sugar and pressure together, and these two factors are major contributors to cardiovascular risk.”

Mr. Audrys Pauza, a British Heart Foundation-funded PhD student in Professor David Murphy’s lab in the Bristol Medical School and lead author on the study, added: “The prevalence of diabetes and hypertension is increasing throughout the world, and there is an urgent need to address this.

“Drugs targeting the GLP-1 receptor are already approved for use in humans and widely used to treat diabetes. Besides helping to lower blood sugar these drugs also reduce blood pressure, however, the mechanism of this effect wasn’t well understood.

“This research revealed that these drugs may actually work on the carotid bodies to enact their anti-hypertensive effect. Leading from this work, we are already planning translational studies in humans to bring this discovery into practice so that patients most at risk can receive the best treatment available.”

But GLP-1 is just the start. The research has revealed many novel targets for ongoing functional studies that the team anticipate will lead to future translational projects in human hypertensive and diabetic patients.

Reference: “GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition” by Audrys G. Pauza, Pratik Thakkar, Tatjana Tasic, Igor Felippe, Paul Bishop, Michael P. Greenwood, Kristina Rysevaite-Kyguoliene, Julia Ast, Johannes Broichhagen, David J. Hodson, Helio C. Salgado, Dainius H. Pauza, Nina Japundzic-Zigon, Julian F.R. Paton and David Murphy, 1 February 2022, Circulation Research.

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Following the above article, I wrote a comment on the above finding to Professor Andrew which motivated another mechanical engineer friend of mine Mr. Silvanus in the same WhatsApp group to write me a letter asking me this question below:

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Dear Professor Dr Ju Boo Lim

I read with great interest your comment to what Professor Andrew sent to us about this LGP 1 enzyme or whatever that is I have no clue that can control our high blood pressure

May i seek your highly learned medical knowledge if doctors have been wronged all these years giving us the wrong medication with all those high blood pressure and diabetes pills to treat these two diseases when they should have used this body enzymes GLP 1 whatever that is, to naturally treat high blood pressure and diabetes

I await your most learned answer

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I then replied to Mr. Silvanus this:

Thank you, Mr. Silvanus, for your confidence in me attempting to handle this difficult question of yours

I think it is best i solicit the answer or opinion from other doctors in this chat here instead of me attempting to field your question

That way we can learn from each other and share our knowledge together 

But if there is no response from other doctors or medical or scientific expertise only then shall I try to answer within a day or two

You have really confronted me with a very good question though a very difficult challenge 

We shall try our best

Lim jb

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I  waited for two days for other doctors  to reply to Mr. Sivanus. Unfortunately, even though there were quite a number of medical specialists and scientists in the chat group, but none answered  

So, I decided to reply to Mr. Silvanus instead of waiting further. Here’s what I think just to share with other readers in this blog

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Before I begin my explanation, I would also like Professor Andrew who sent us this article by Professor Julian Paton to comment with some good well-explained details after reading my comment below.

Since no one, especially medical doctors, pharmacologists or molecular biologists have responded to my request on your earlier question for me, whether or not doctors have taken the wrong approach in treating high blood pressure and diabetes using drugs instead of this natural protein from the body itself here are my views.

Our current trend of using antihypertensive agents to treat hypertension, such as the selective use of any of the range and generations of these drugs, starting with diuretics as first- line, onto the use of beta-blockers, ACE inhibitors, calcium channel blockers, angiotensin II receptor blockers, alpha blockers, alpha-2 receptor agonists or other blockers we know of, is the best doctors can offer for the present at least as an interim measure especially if the disease is severe and uncontrollable. But we need to look at better ways such as changing the ways we live if they are mild We shall discuss this later. 

Neither is it the best doctors can offer to treat maturity onset diabetes using of non-insulin dependent oral antidiabetic drugs such as the more popular biguanides (metformin), or sulfonylureas (glimepiride), meglitinides (repaglinide), dipeptidyl peptidase IV inhibitors, thiazolidinediones, and alpha-glucosidase inhibitors…etc, etc. 

We shall explain why genes can be influenced by environmental factors, and we can slowly wean ourselves from drug dependence if we can modify or prevent these environmental exposures. We shall discuss this further towards the end

In the meantime we have been using these classes of drugs for some time now based on our current understanding on how these medicines work (mode of action or pharmacodynamics) before new discoveries like GLP-1 surfaced to change our ways of thinking in treating these two disorders.

Doctors merely follow standard protocols based on previous knowledge, not new discoveries they are unaware of

The discovery by an international team of scientists that this glucagon-like peptide (GLP-1) has been shown to be capable of controlling blood pressure and blood sugar is something new to me even as a research doctor and scientist, and I don’t expect other doctors to know this.

In the absence of new findings until lately, we don’t expect doctors to know new avenues in managing hypertension and diabetes except using drugs.

Neither do we expect drug companies to know this. Even if they do, it is highly unlikely they will be willing to promote a natural protein expressed by the body to be used. Naturally they want them to be drug-based for their multi-billion-dollar profit and patency.

GLP-1 mentioned in the discovery is a gene expression, meaning it is a specific protein expressed by a specific gene, and it is these peptides that influence blood pressure and sugar levels.

Then again, I personally have two questions myself for these international team of esteemed scientists to answer:

Firstly, in what way does this specific protein lowers blood pressure if high? Of course, in general we know the plasma proteins in the blood maintains and stabilize blood pressure through its viscosity, high density and hydrostatic actions, but they don’t lower blood pressure for those who are hypertensive

Secondly, in my understanding in physiology and medicine, Professor Julian Paton, senior author of the study did not tell us the type of carotid bodies in the neck were responsible. She only mentioned carotid bodies

There are actually two types of carotid bodies, namely the baroreceptors (pressure sensors) and the chemoreceptors (chemical receptors). Hence which between the two is responsible for lowering blood pressure, surely not the chemoreceptors?

Before I ask my 3 or 4 other questions for Professor Julian Paton, let me explain what these receptors are for non-doctors in this chat group on baroreceptors and chemical receptors.

Let me explain so that we can carry on answering your question Mr. Silva. 

Baroreceptors are alternatively called mechanoreceptors that relay information about blood pressure within the autonomic nervous system. Information is then passed in rapid sequence to alter the total peripheral resistance and cardiac output, maintaining blood pressure within a preset, normalized range.

Just as an example, these baroreceptors are instantly triggered in the event of hypovolemic shock due to say massive bleeding where the blood pressure dips dangerously low

The body then compensates by increasing heart rate and cardiac output. They are abundantly found in the wall of the bifurcation of the internal carotid arteries (carotid sinus) and in the wall of the aortic arch.

The key difference between baroreceptors and chemoreceptors is that baroreceptors are mechanoreceptors responding to blood pressure changes while chemoreceptors are cells sensing the concentration of chemicals in the surrounding extracellular fluid such as pH levels, carbon dioxide, sugar and hormonal levels. Both receptors exert great influences on the autonomic control of the heart and blood vessels to bring about cardiovascular changes and their adjustments

But I am unsure how GLP-1 peptides work on baroreceptors, a question we need Prof Julian to answer

We may be able to offer some theories on how they being a protein is able to regulate sugar levels?

These are the questions I personally have for Professor Julian and her team of international scientists although Mr Silva was asking me a different question

My understand in this area is that these receptors responsive to changes in blood pressures and chemical changes such as carbon dioxide and pH in the blood (I am not sure about blood sugars) are not only found in the carotid region of the neck, but elsewhere in the blood vessels such as in the aortic arch near the heart.

Would this GLP-1 also excite these receptors elsewhere in the body or only specifically in the neck region as Prof Julian mentioned?

Secondly, baroreceptors are responsive only to changes to pressures, and I do not think a protein like GLP-1 can control blood pressure variations. In what way and its mechanisms?

Thirdly, my question for Professor Julian Paton and her international team of scientists is, though very probable these small molecule peptides can alter sugar levels, we need to know the biochemical pathways and mechanisms of their feedback.

In short, how do these peptides GLP-1 influence gene expression of the beta-cells of the Islets of Langerhans in the pancreas to secrete insulin, which of course control sugar levels? This is my question to her.    

Fourthly, whether or not we use drugs or natural gene (protein) expressions like GLP-1 to control high blood pressure or glucose levels as our preferred therapeutic modality, we still need go back to square one that gene expression is very much influenced by external environment on phenotype (genetic behaviour), endocrine behaviour, diseases onset and outcome of diseases. We already knew this long ago.

As far as I know there could be as much as 30 million on and off genetic switches inside just 2 percent of the human genomes and these off and on switches control those genes encrypted within the remaining 98 percent of the genome. Hence the picture would be far more complicated

It is these external environmental factors that shall have the final say on those GLP-1 expression or those drugs we mentioned on arterial or endocrine events Julian and her teams were excited about.     

Gene regulation can occur at any point during gene expression, although mainly at the level of transcription (when the information in a gene’s DNA is passed to mRNA). Signals from the environment internal and external or from other cells activate proteins called transcription factors.

 These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription.

By controlling the level of transcription, this process can determine when and how much protein such as GLP-1 probably is expressed (translated or made) by the gene, and hence the chance of disease emerging and their outcome

But this process depends much on the environment and our lifestyles especially nutrition

This discovery by Professor Julian and her team of international scientists make tremendous sense to me as it explains why lifestyles and dietary modifications are far better and more permanent solutions than using drugs to manage high blood pressure 

By controlling the level of transcription, this process can determine when and how much protein such as GLP-1 probably is expressed (translated or made) by the gene, and hence the chance of disease emerging and their outcome

But this process depends much on the environment and our lifestyles especially nutrition

Hence, in my view in a nutshell since you have asked, it is still not wrong for doctors to prescribe those drugs in the past and even now because they use them based on previous discoveries by other scientists and what was offered to them by drug companies. But drugs do not cure the root causes causing the genes to express themselves differently

Doctors don't produce drugs. They were only given to them to use for patients. Doctors also would not know anything about natural GLP-1 expression if it is a safer and more effective modality over drugs.

This said, it is still strongly the modification of our diet and lifestyles and environmental influences on gene expression that has the final say on how these two conditions need to be managed. 

In short, known as epigenetic factors, it is the internal and external environmental influences such as diet, stress, anger, meditation, relaxation, sedentary lifestyle, smoking, obesity, exercise and physical activities, free radical damages...etc  on the genes that will have an impact on how genes are going to express themselves such as GLP-1 and theses changes are reversible unlike genetic changes that changes the DNA sequence irreversibly.  

Not surprisingly, the GLP-1 production may in turn have an impact on blood pressure and blood sugars level. 

In other words, it is still the epigenetic dietary, environmental factors, the way we live that finally determine whether or not will be prone to getting hypertension and diabetes.

This means it would be far better to control these external and internal environmental influences on the genes for a true and permanent solution to these two conditions rather than to depend on drugs that serves as short term solution since the root causes were never addressed. Drugs temporary alter, inhibit or replace the continuous flow of a chemical pathology and need to be taken continuously daily to block their continuous flow, but they do not offer a permanent cure. 

Changing the ways how our genes react would be the best practice in health and medicine. Preventive medicine is of course far better than curative medicine by understanding the root causes of diseases and how to address them instead of using drugs to mask and suppress to "control" the disorder. 

Needless to say, it is not the drugs prescribed that are going to offer a permanent solution to hypertension and diabetes but it is our lifestyle, nutrition, internal and external environment that matters

All these while we know that bad lifestyles are the main cause of hypertension and diabetes, but we do have a proper explanation until now.

 Hence, we depend mainly on drugs given by doctors to "cure" hypertension and diabetes until this discovery

My opinion is, this discovery by a team of international esteemed scientists led by Professor Julian Paton is an eye opener and make tremendous scientific sense to me

I hope I have enlightened and answered your question Mr. Silva.

We would like Professor Andrew who sent us this article to comment further with good explanatory details. He knows more than me

Over to you Professor Andrew

Regards,

lim ju boo 

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Following the above article, Professor Dr. Andrew Charles Gomez commented using WhatsApp this:

"Yes Prof JB 

Epigenetic factors play a vital part in the control of our health. I agree drugs helps in the initial stages. 

But lifestyle changes are important in the mainstream stage with some help from medication" 

Thanks. 

Andrew Gomez