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Revolutionary diabetes treatments will now be tested in clinical trials

The type 2 diabetes’ epidemic is worsening. Tore Bengtsson, from Stockholm University, is working on three innovative treatments, of which two will now be tested in clinical trials.

Insulinspruta
Many people with type 2 diabetes are treated with insulin syringes. But there is a big problem, in type 2 diabetes the body reacts poorly to insulin. Therefore, insulin has never worked very well as a treatment for type 2 diabetes.
Photo: Andrey Popov/Mostphotos

Most researchers would be happy if they found one new way to treat the epidemic disease of type 2 diabetes. Tore Bengtson, professor at the Department of Molecular Biosciences, the Wenner-Gren Institute, is working in parallel with no fewer than three different forms of treatment, all of which have the potential to reverse the disease.
“This epidemic can be likened to an invisible, slow-motion train derailment, with enormous negative effects on the health of the affected individuals. I want to help buck this trend,” he says.

He discovered the first treatment method by pure chance, with his then-doctoral student, Anette Langebäck. During a visit to a laboratory in Australia, they studied how muscle cells absorb sugar – glucose – from their surroundings. This function is important in lowering our blood sugar after a meal, but works poorly in people who have type 2 diabetes.

They exposed the muscle cells to a substance that was originally developed to stimulate fat cells. The expectation was that nothing special would happen to the muscle cells, but suddenly they began to absorb glucose.
“Anette came and told me that the test had failed, that something must have gone wrong. But I said – what if something hasn’t gone wrong? What if we’ve discovered a new way of getting these cells to absorb glucose?” says Tore Bengtsson.

 

A new way to lower blood sugar in diabetics

And so it was; the relatively unplanned experiment had been unusually successful. Researchers had previously thought that the major way to enable muscle cells to absorb sugar from the blood was to stimulate them with insulin, a hormone. This is why many people who have type 2 diabetes are treated using insulin injections. However, there is a significant problem with this method: in type 2 diabetes, the body reacts poorly to insulin. This is part of the clinical picture, so insulin has never been particularly effective as a treatment for type 2 diabetes.

The fundamental discovery made by Tore Bengtsson’s research group is that a specific receptor on the surface of the muscle cells, the beta-2 adrenergic receptor, can also trigger the cells to absorb sugar.
“When the beta-2 adrenergic receptor is stimulated, the muscles absorb more glucose and blood sugar decreases,” says Tore Bengtsson.

After this unexpected discovery over a decade ago, these researchers have proven that this new mechanism can be used to treat type 2 diabetes in animal trials. Tore Bengtsson hopes the pharmaceutical company Atrogi, which he co-founded, will be able to start clinical trials in 2022.
“We have a candidate pharmaceutical that has undergone toxicological studies and are now applying for approval for the study,” he says. 

 

Brown fat can transform blood sugar into heat

Tore Bengtsson
Tore Bengtsson hopes the pharmaceutical company Atrogi, which he co-founded, will be able to start clinical trials on a candidate pharmaceutical in 2022.

The other potential treatment for type 2 diabetes that Tore Bengtsson has discovered builds upon a relative of the beta-2 adrenergic receptor, called the beta-3 adrenergic receptor. This also triggers cells into absorbing sugar, but is found on the surface of something called brown fat. This type of fat has cells that have decoupled their power plants, the mitochondria. Instead of generating energy, they create heat.

When brown fat is stimulated via the beta-3 adrenergic receptor, the cells send special receptors, GLUT-1, to their surfaces. These receptors then hoover up sugar from the blood. “They’re just like vacuum cleaners, pumping glucose into the brown fat,” says Tore Bengtsson.

His research group has successfully shown that this mechanism can be used to lower blood sugar levels in mice. They are now looking for molecules that can be used as pharmaceutical candidates in clinical trials.

 

Porous silica particles can slow digestion

Molecular traps
Mesoporous silica particles. The particles are harmless and pass through the gastrointestinal tract intact and can be given as a fine powder dissolved in, for example, water together with the food you eat. The particles act as "molecular traps" in the intestine and capture digestive enzymes. This leads to a slower breakdown of food and thus to lower glucose and insulin peaks in the blood.

The third treatment that Tore Bengtsson has developed to counteract type 2 diabetes involves slowing down food digestion. He has developed a type of powder that consists of porous microparticles of silicon, the material found in sand. These particles are full of tiny holes, just the right size to capture enzymes that break down fat and carbohydrates in the digestive tract. So if someone swallows a few grams of this powder with a meal, the food will be digested more slowly.
“Today’s fast food will then become slow food. This lowers the glucose peaks in the blood and the total uptake of energy from the gut is also reduced,” says Tore Bengtsson.

A pilot study of 43 people with early signs of type 2 diabetes showed that this treatment can lead to positive outcomes without any major side-effects. The trial participants drank the powder before each meal for twelve weeks, which led to an improvement in numerous symptoms and to reduced levels of blood sugar.

In 2022, Sigrid Therapeutics, another company co-founded by Tore Bengtsson, will start a larger scale study of the powder. The hope is that type 2 diabetes can be prevented in people who are at risk of developing this disease.

“I’m frequently asked why people can’t just eat less and move more. But people don’t do this. Many find it hard. I want to help the people who can’t manage it, so they don’t develop this disease,” says Tore Bengtsson.

Read more on Tore Bengtsson´s research.

Text: David Finer/Ann Fernholm