A single exercise session is enough. Is it thanks to mTORC1?
Magnus Romme Larsen’s ultimate goal is to develop exercise in a pill for people who cannot physically exercise enough to increase insulin sensitivity.
A series of studies have shown that just a single exercise session increases insulin sensitivity in the muscles – an effect that helps improve the ability to control the blood sugar level in the subsequent days. But what is going on? What are the molecular mechanisms underlying this beneficial effect on health? MSc student Magnus Romme Larsen – graduating in September – will spend the next 3 years of his life finding out, with the long-term aim of enabling development of a drug for those who cannot themselves exercise sufficiently.
He will do this in a PhD project at the University of Copenhagen’s Department of Nutrition, Exercise and Sports, for which he has just received a grant of DKK 1.1 million from the Danish Diabetes Academy.
The theory: the answer is mTORC1 signalling
The theory that Magnus Romme Larsen and his supervisor, Professor Jørgen Wojtaszewski, are working on is that the answer is mTORC1 signalling. Mass spectrometry studies of human muscle biopsies from the group of Professor Wojtaszewski’s have identified mTORC1 signalling as a link between insulin-induced and exercise-induced signalling for improved glucose uptake in the muscles used. If it turns out that their hypothesis holds up, the prospect is that drugs can potentially be developed that will specifically emulate the positive effects of physical activity, thus raising the insulin sensitivity of the musculature. In other words: exercise in pill form for people who cannot themselves do enough physical exercise.
Obtaining the information that Magnus Romme Larsen will be looking for is a matter of great importance: the skeletal musculature is responsible for the majority of glucose uptake and accounts for up to 80% of insulin-stimulated sugar uptake throughout the body.
Magnus Romme Larsen explains that the industry is very interested in this improvement in insulin sensitivity after physical activity, but that lack of knowledge of the underlying molecular mechanisms has so far prevented it making use of this biological phenomenon.
One of the trials he is about to start work on involves using a drug to block mTORC1 in 12 healthy young men before letting them perform exercise with one leg for 2 hours. He will measure their insulin sensitivity after 4 hours, and his expectation is that, by blocking mTORC1, he will be able to turn off the positive effects of physical activity. Ultimately, the expectation is that this will enable us to learn more about the relationship between physical activity, muscular insulin sensitivity and improved blood sugar control.
Potential benefit for people with diabetes
Magnus Romme Larsen already works at the University of Copenhagen’s Department of Nutrition, Exercise and Sports with Professor Jørgen Wojtaszewski, who will be his principal supervisor during the PhD project. Professor Wojtaszewski is very happy that Magnus is now assured of a grant and hence of the space to focus on his work. ‘The research is a unique opportunity to obtain new knowledge. If our hypothesis about mTORC1 playing a key role in the regulation of insulin sensitivity is confirmed, it will potentially benefit people living with diabetes. The industry has already shown interest and curiosity about the research – among other things, because the project will contribute to knowledge of the cellular signalling mechanism around insulin sensitivity, which may prove fundamental to the development of a drug targeting reduced insulin sensitivity in muscle tissue’, he says.
Collaborating with partners Down Under
In the course of his PhD project, Magnus Romme Larsen will travel to the University of Sydney for a spell to work with Professor David James in what is acknowledged to be one of the world’s best centres of mass spectrometry research. Professor James collaborates closely with Jørgen Wojtaszewski and has been involved in the preliminary trials that stimulated interest in mTORC1. The purpose of Magnus’s visit to Australia is to study comprehensive biochemical analyses of biological material collected from the human trial carried out in Denmark.
Magnus Romme Larsen
Tel: +45 40 18 62 74
Danish Diabetes Academy
Managing Director Tore Christiansen
Tel: +45 29 64 67 64