Important breakthrough!

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Why do high blood pressure and diabetes always coexist? Why can the new hypoglycemic drug GLP-1RA bring blood pressure benefits? Recently, the research report published in the journal Circulation Research not only gave the answers to the above questions, but more importantly pointed out that the "GLP1-CBs pathway" may become a new target for diabetes-hypertension treatment! Unraveling the mystery Diabetes and hypertension are common comorbidities, and the two often maintain a close relationship, but the reasons behind them are not yet known
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Recently, an international team of researchers from the University of Bristol in the United Kingdom and the University of Auckland in New Zealand finally solved this long-standing mystery.
The study showed that glucagon-like peptide-1 expressed in the carotid body (CB) is affected by GLP1R plays an important role in regulating blood pressure and blood sugar at the same time, and the decreased expression may be one of the important reasons for the combination of hypertension and hyperglycemia
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It was further found that GLP1 can regulate the peripheral chemoreflex acting on the carotid body.
In hypertensive patients with diabetes, the "GLP1-CBs pathway" may become a new therapeutic target for controlling metabolic disease states and hypertensive sympathetic nerve activity
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The deep link between hyperglycemia and hypertension - carotid body, GLP1R and GLP1 It is well known that after eating, GLP1 is released from the intestinal wall to stimulate the pancreas to secrete insulin and play a role in controlling blood sugar
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The study found that GLP1 also stimulates the carotid body in the neck, an important chemoreceptor involved in the body's blood pressure regulation
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 Carotid body: An important chemoreceptor in the human body, it is an oblate corpuscle, 3-5 mm in diameter, located behind the bifurcation of the internal and external carotid arteries, and connected to the arterial wall by connective tissue
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The nerve impulses emitted by the carotid body chemoreceptors are conducted along the sinus nerves to the respiratory and cardiovascular centers of the medulla oblongata, and reflexively regulate the activity of the respiratory (main) and cardiovascular systems
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 The team from the University of Bristol used a high-throughput genomics technique called RNA sequencing to read genetic information in the carotid bodies of rats with and without hypertension
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 The researchers found that GLP1R expression in the carotid body is associated with increased peripheral chemoreflex sensitization under conditions of elevated blood pressure and altered glucose metabolism
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Exogenous and endogenous ligands acting on GLP1R were demonstrated to modulate tSNA through carotid body chemoreceptor inhibition by local delivery of selective GLP1R agonists/antagonists to the carotid body
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The study further showed that activation of GLP1R in the carotid body attenuated its reflex sensitivity and reduced tonic afferent drive from peripheral chemoreceptors in the homeostatic response to high glucose
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This inhibitory effect also exists after systemic administration of GLP1R agonists
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To this end, the researchers propose a novel mechanism whereby, in healthy conditions, GLP1 prevents chemoreflex-mediated sympathetic activation during the postprandial period in response to elevated glucose and/or insulin levels
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 Professor David Murphy, from the Bristol Medical School, explained: "Mapping this link requires genetic mapping and multiple validation steps
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We never thought GLP1 would be on the 'radar', which is very impressive excited and lead to new directions of exploration for future therapeutic strategies
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"Fig.
1 GLP1R is expressed in human carotid bodyFig.
2 GLP1R regulates sympathetic nerve activityFig.
3 Activation of GLP1R inhibits chemoreflex-induced arterial blood pressure response"GLP1-CBs pathway" may become a new target for diabetes-hypertension therapy" People with high blood pressure and/or diabetes are at high risk for life-threatening cardiovascular disease
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A large number of patients will remain at high risk even while receiving medication
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This is because most medications only treat the symptoms, not the underlying causes of high blood pressure and high blood sugar
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We have known for a long time that high blood pressure and diabetes are closely linked, and now we have finally discovered the cause
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The carotid body is the 'convergence point' for GLP1 to control both blood sugar and blood pressure, and is coordinated by the nervous system where the carotid body acts
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Professor Julian Payton, of the Heart Research Centre at the University of Auckland, said of the study
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 Professor Rod Jackson, an epidemiologist at the University of Auckland, said: "Blood pressure in people with hyperglycemia is often difficult to control, so these findings are very important.
By administering GLP1, it may be possible to reduce both blood sugar and blood pressure, both of which are major factors in cardiovascular disease
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Drugs targeting the GLP1 receptor have been approved for the treatment of diabetes
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In addition to helping to lower blood sugar, these drugs can also lower blood pressure, but the mechanism of their blood pressure lowering action is not well understood
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This study suggests that these drugs may act on the carotid body to exert their antihypertensive effects
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Guided by this work, we have planned human translational studies to put this discovery into practice so that relevant patients can receive optimal treatment options
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This study found that the glucagon-like peptide-1 receptor (GLP1R) expressed in the carotid body plays an important role in regulating blood pressure and blood sugar at the same time, and the decreased expression may lead to the combination of hypertension and hyperglycemia It is one of the important causes of seizures
.
It
was further found that GLP1 can regulate the peripheral chemoreflex acting on the carotid body.
In hypertensive patients with diabetes, the "GLP1-CBs pathway" may become the control of metabolic disease states and hypertensive sympathetic nerve activity.
A new therapeutic target
for .

Reference: [1]University of Bristol.
Sweet pressure: Scientists discover link between high blood pressure and diabetes[EB/OL].
sciencedaily.
com/releases/2022/02/220201074528.
htm.
[2]Audrys G.
Pauza,Pratik Thakkar,Tatjana Tasic,et al.
GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition[J].
Circulation Research.
2022 ;0:CIRCRESAHA.
121.
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