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.
……………………
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.
……………………………………..
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:
…………………………………………
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
……………………………………………………
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
…………………………………………….
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
…………………………………………………:
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
