An international team of researchers, led by the universities of Bristol, UK, and Auckland, New Zealand, has finally uncovered the long-standing mystery of why many patients with high blood pressure (hypertension) also suffer from diabetes (high blood sugar).
This significant discovery reveals that a small protein cell, glucagon-like peptide-1 (GLP-1), plays a crucial role in linking the body’s regulation of blood sugar and blood pressure.
Professor Julian Paton, a senior author and Director of Manaaki Mãnawa – The Centre for Heart Research at the University of Auckland, stated: “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 1 February, involved contributions from scientists in Brazil, Germany, Lithuania, and Serbia, alongside those in the UK and New Zealand.
GLP-1 is released from the gut wall after eating and stimulates insulin production from the pancreas to control blood sugar levels. Previously known, the new discovery shows that GLP-1 also activates a small sensory organ called the carotid body in the neck.
The University of Bristol team utilized RNA sequencing, an unbiased, high-throughput genomics technique, to read all the gene messages expressed in the carotid body in rats with and without high blood pressure. This led to the finding that the receptor sensing GLP-1 is located in the carotid body, though it is less present 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.”
Patients with hypertension and/or diabetes are at high risk of life-threatening cardiovascular disease. Even with medication, many remain at high risk because most treatments address only symptoms rather than the underlying causes of high blood pressure and high sugar.
Professor Rod Jackson, a world-renowned epidemiologist from the University of Auckland, noted: “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 Pauža, 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.”
GLP-1 is just the beginning. The research has identified many novel targets for ongoing functional studies, which the team anticipates will lead to future translational projects for patients with hypertension and diabetes.
The study was funded by the British Heart Foundation and the Health Research Council of New Zealand.
