Researchers hope to improve medical treatment for diabetes and obesity

It made things a bit easier and improved the quality of life of millions of people suffering from diabetes when researchers in the 1990s and 00s invented the drug that stimulates the receptor of the intestinal hormone GLP-1. This revealed that there was more than one treatment for the disease, and that it did not necessarily involve injecting pure insulin into the body. And now there may be more good news on the way.

In many ways, it is kind of amazing to think that a GIP-targeted drug will soon be available in the market, because basically all pharmaceutical engineering involving GIP has been done without a structure or model of the GIP receptor.

Because it turns out that the effect of the drug is significantly improved if it targets both the GLP-1 receptor and its sister at the same time. And now researchers from the University of Copenhagen have shown precisely how the GIP receptor can be targeted.

‘You can say that GLP-1-targeted drugs have eclipsed GIP, because they work so well. But seeing as both diabetes and obesity continue to be a problem throughout the world, there appears to be a continued need for even better medical treatment. And GIP seems to be the way forward’, explains Professor Mette Rosenkilde from the Department of Biomedical Sciences.

Blind pharmaceutical engineering

Together with her colleagues at the Novo Nordisk Foundation Center for Basic Metabolic Research, Thomas Frimurer and Michael Luckman, she has shown precisely how the GIP receptor works at the molecular level and how it can be regulated.

‘In many ways, it is kind of amazing to think that a GIP-targeted drug will soon be available in the market, because basically all pharmaceutical engineering involving GIP has been done without a structure or model of the GIP receptor. We did not have a manual for understanding its activities. This is what the new study can provide’, she says.

For example, she explains, it has been a bit of a mystery to the researchers why the GIP receptor works really well when paired with GLP-1, both when activated and shut down. 

But with the new study, the researchers have come a step closer to understanding just that.

Built with a computer, confirmed in the lab

The new mapping is the result of a cross-disciplinary collaboration. First, the researchers ‘built’ the receptor using a computer programme and simulated interactions based on the built model.

They then went back to the lab to confirm their findings by looking at a human cell and studying some of the same mechanisms in a petri dish.

The researchers hope the new findings will lead to new and improved obesity and diabetes drugs targeted at both GIP and GLP-1, but they also know that this kind of pharmaceutical engineering takes years.  

Read the entire study: ‘Investigating GIPR (ant)agonism: A structural analysis of GIP and its receptor’, in the scientific journal Structure.

The company Antag Therapeutics ApS has contributed to the new study.

Contact:

Professor Mette Rosenkilde
+45 30 60 46 08
rosenkilde@sund.ku.dk

Journalist and Communications Consultant Mathias Traczyk
+45 93 56 58 35
mathias.traczyk@sund.ku.dk