Link between high blood pressure, diabetes finally solved: Gut protein to blame

A protein that fuels high blood pressure and diabetes has been identified by scientists, explaining the link between the two. It shows why the potentially deadly conditions often go hand in hand, opening the door to the development of better therapies.

Most people with diabetes will eventually have high blood pressure, or hypertension, along with other heart and circulatory problems. This can lead to many complications, including eye and kidney disease, or make the conditions worse.

“We have known for a long time hypertension and diabetes are inextricably linked,” says senior author Julian Paton, director of Manaaki Mãnawa – The Centre for Heart Research – at the University of Auckland, in a statement. “We have finally discovered the reason, which will now inform new treatment strategies.”

The protein, called GLP-1 (glucagon-like peptide-1), is released from the wall of the gut after eating. It triggers the glucose controlling hormone insulin from the pancreas, and also boosts the carotid body in the throat. The tiny organ is extremely sensitive to oxygen, helping to regulate blood pressure.

Learning more about the GLP-1 receptor

Experiments in rats found the receptor that senses GLP-1 was less effective in those with high blood pressure. A state of the art scanning technique called RNA sequencing read all the messages of expressed genes in the carotid body.

“Locating the link required genetic profiling and multiple steps of validation,” explains senior author David Murphy, a professor of experimental medicine at the University of Bristol. “We never expected to see GLP-1 come up on the radar. This is very exciting and opens many new opportunities.”

Adds lead author Audrys Pauza, a student in Murphy’s lab: “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 was not well understood. This research revealed these drugs may actually work on the carotid bodies to enact their anti-hypertensive effect.

It’s estimated that more than 37 million people — about 11.3% of the population — have diabetes in the U.S., according to the Centers for Disease Control and Prevention. Most have the type 2 form linked to unhealthy lifestyles.

Meanwhile, 2018 estimates by the American Heart Association show more than 103 million in the nation have high blood pressure. A significant portion are still undiagnosed, as there are no symptoms. The “silent killer” can cause heart attacks and strokes.

“The carotid body is the convergent point where GLP-1 acts to control both blood sugar and blood pressure simultaneously,” says Paton. “This is coordinated by the nervous system which is instructed by the carotid body.”

Future drugs could lower blood pressure, blood sugar at same time

People with hypertension, diabetes, or both, are at high risk of life-threatening heart disease. This remains the case for a large number of patients even when receiving medications. Most drugs only treat the symptoms, and not the cause.

Drugs containing GLP-1could lower blood sugar and blood pressure simultaneously. It would target the root cause of the illnesses, rather than just the symptoms.

“We have known blood pressure is notoriously difficult to control in patients with high blood sugar,” says Rod Jackson, a world renowned epidemiologist from Auckland. “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.”

“Leading from this work, we are already planning translational studies in humans to bring this discovery into practice so patients most at risk can receive the best treatment available,” says Pauza.

It is hoped they will lead to future translational projects in hypertensive and diabetic patients.

The study, funded by the British Heart Foundation and the Health Research Council of New Zealand, is published in Circulation Research.


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