Jakob G. Knudsen

Project title

Mitochondrial control of alpha cell function - Reactive oxygen species, is it control or catastrophy?

What is your project about?

We want to understand the mechanisms that control blood glucose levels. There are, more than 400 million diabetes patients in the world, these patients have lost the ability to control their blood glucose levels. One of the main reasons is that the hormones that normally contribute to the control the blood glucose concentration becomes dysregulated. One of these hormones is called glucagon. Glucagon is, under normal physiological conditions, secreted when we are fasting as a part of the counter regulatory response. The glucagon secreting cells, called alpha cells, can feel when circulating levels of glucose becomes too low. They respond by increasing glucagon secretion, this signals to the liver that glucose production should be increased. However, in patients with obesity or type 2 diabetes, alpha cells are no longer able to correctly regulate glucagon secretion and this leads to higher levels of circulating glucagon, and increase blood glucose levels. While we have known this for some time, we are unable to treat the high glucagon levels in these patients. One of the reasons is that we do not know very much about the glucagon secreting alpha cells and how their function is affected in patients with obesity and type 2 diabetes.

How did you become interested in your particular field of research?

I have been fascinated by cellular metabolism since the beginning of my undergrad studies. However, it was not until my undergrad thesis advisor introduced to exercise physiology that I understood how exciting and complex the interaction between the molecular mechanisms that govern cellular metabolism and the physiological processes that orchestrates whole body energy turn over. This is exactly what makes the alpha cells so interesting, we know very little about the mechanics of how they work, but they have a large influence on whole body metabolism. It is exciting to explore basic mechanisms that have the potential to improve our understanding of human physiology and the treatment and prevention of chronic diseases such as type 2 diabetes.

What are the scientific challenges and perspectives in your project?

The big challenge in this project will be to design the experiments that will show the molecular mechanisms that underlie alpha cell function. It is not straightforward to study alpha cells they are part microorganisms in the pancreas. The micro organs consist of not only alpha cells, but also other cell types that secrete other hormones, so to understand how alpha cells work we need to use specially designed methods to recognize them and be aware of the complex interaction that takes place between the different cells types in the individual micro organ. While, we have already developed a large number of methods to examine the alpha cells and this project will no doubt add more methods to our toolbox.

What is your estimate of the impact, which your project may have to society in the long term?

There are almost 300.000 danes living with type 2 diabetes, and while we may be studying basal mechanisms, the discoveries made in this project may in the long run have impact on the lives of patients. We hope that the mechanisms we investigate in this project will contribute to the discovery of new medicines directed towards alpha cells and the increased glucagon levels in patients with diabetes.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

Being supported by the Sapere Aude program is an invaluable contribution to developing and expanding my research group. The grant also allows me to continue to develop as an independent researcher. We now have the opportunity to go completely in depth and focus 100% on answering some very exciting scientific questions.

Background and personal life

I live in Frederiksberg with my partner Vibe. When I am not investigating alpha cells, reading interesting research papers or spending time with family and friends, I spend my time in Sweden, where we are currently renovating our farm.