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 Mãnawa -- 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 in Circulation Research [1 February 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 Rod Jackson, an 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 Pauža, a British Heart Foundation-funded Ph.D. 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 discover 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.

The study was funded by the British Heart Foundation and the Health Research Council of New Zealand.

As with anything you read on the internet, this article should not be construed as medical advice; please talk to your doctor or primary care provider before making any changes to your wellness routine.

Materials provided by:

https://www.bristol.ac.uk/news/2022/february/blood-pressure-diabetes.html

https://www.bristol.ac.uk/

http://dx.doi.org/10.1161/CIRCRESAHA.121.319874

https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.319874

Abstract

High cereal fiber intake is associated with reduced risk for type 2 diabetes, but wheat fiber had little or no effect on glycaemic control or oral glucose tolerance in clinical trials lasting 4-12 weeks. To explain this discrepancy, we hypothesised that colonic adaptation to increased wheat fiber intake takes many months but eventually results in increased SCFA production and glucagon-like peptide-1 (GLP-1) secretion. Thus, the primary objective was to determine the time-course of the effects of increased wheat fibre intake on plasma acetate, butyrate and GLP-1 concentrations in hyperinsulinaemic human subjects over 1 year. Subjects with fasting plasma insulin >or= 40 pmol/l were randomly assigned by computer to receive either a high-wheat fibre cereal (fibre group; 24 g fibre/d; twenty assigned; six dropped out, fourteen included) or a low-fibre cereal (control group; twenty assigned; six dropped-out, fourteen included) daily for 1 year. Acetate, butyrate and GLP-1 were measured during 8 h metabolic profiles performed every 3 months. There were no differences in body weight in the fiber group compared with the control group. After 9 months baseline-adjusted mean 8 h acetate and butyrate concentrations were higher on the high-fibre than the control cereal (P < 0.05). After 12 months on the high-fiber cereal, baseline-adjusted mean plasma GLP-1 was 1.3 (95 % CI 0.4, 2.2) pmol/l (P < 0.05) higher than at baseline (about 25 % increase) and 1.4 (95 % CI 0.1, 2.7) pmol/l (P < 0.05) higher than after 12 months on control. It is concluded that wheat fiber increased SCFA production and GLP-1 secretion in hyperinsulinaemic humans, but these effects took 9-12 months to develop. Since GLP-1 may increase insulin sensitivity and secretion, these results may provide a mechanism for the epidemiological association between high cereal fiber intake and reduced risk for diabetes.

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Grant support

• OOP-64648/Canadian Institutes of Health Research/Canada

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