You have to be persistent and confident
On the door of Bryndis Birnir´s office it says "Neuroscience", but her research also touches on diabetes. She has shown that the brain´s most important inhibitory neurotransmitter GABA (gamma-aminobutyric acid) also plays a part in regulating blood glucose levels and affects immune system cells.
Bryndis Birnir is professor at the Department of Neurosciences at Uppsala Biomedical Center. She is one of the scientists who collaborate with Lund University Diabetes Centre (LUDC) in the EXODIAB project (see link below). "As insulin-producing beta cells secrete GABA, GABA must have a role to play and this is what I wanted to map", says Bryndis Birnir.
A bridge between alpha and beta
Bryndis Birnir describes GABA-role in glucose regulation as the bridge between alpha and beta cells, i.e. between the alpha cells that raise blood glucose levels and the beta cells that bring them down. It is primarily GABA-role relating to brain function that has been explored. Various drugs that treat insomnia, anxiety and epilepsy, for example, work by activating the contact points of GABA in the brain.
GABA affects different types of cells in different parts of the body. However, the substance always slows down activity. "It is obvious that a neurotransmitter that affects activity from several different types of cells must be of great importance", says Bryndis Birnir.
Seemingly negligible amounts
"The amount of GABA around the nerve cells and probably also around the insulin-secreting beta cells is approximately one million times lower than the amount of GABA that is secreted in the synapses between the brain´s nerve cells", explains Bryndis Birnir. She adds that the almost negligible levels of GABA are very important for cellular activity. Although Bryndis Birnir was convinced of the significance of the low GABA levels other scientists were initially very sceptical. "The last piece of evidence came about when we collated all our data and saw a very clear association on the screen. All of a sudden all pieces came together, but it took 20 years for the rest of the scientific world to reach the same conclusion.
Adjusting the balance
GABA is also important in relation to diabetes. The substance is secreted from beta cells. Their counterparts, the alpha cells, sense this and decrease their own activity. As a result, the alpha cells secrete less of their hormone, glucagon, which is the hormone that raises blood glucose levels. "People with type 2 diabetes have too much glucagon which is one of the main reasons for their raised blood glucose leves", says Bryndis Birnir, who also explains the objective of her diabetes research: "If we can influence GABA and the balance between beta and alpha cell activity in experiments, and at a later stage in drug trials, we could create a useful tool for the treatment of type 2 diabetes".
A life with GABA
Work is on-going, partly through experiments on animal cells and partly on donated increases from deceased subjects. "Rats and mice are very different to humans. The dissimilarities are many and therefore it is very important that we are also able to study human cells", explains Bryndis Birnir. Because GABA affects so many different types of cells, the road to a working drug for treating, for example, diabetes is complex. The aim is to influence beta and alpha cells but not other cells, such as the nerve cells in the brain, as this would result in undesirable effects. "Perhaps there are already such drugs that work on diabetes but in much smaller doses".
Bryndis Birnir´s life with GABA, as she puts it, began in 1991 in Canberra, Australia and with the biophysicist Peter Gages. "He worked with ion channels and this had also become the focus of my research", she explains.
Fascinated by physiology
It was clear early on that Bryndis Birnir was going to work with in the field of natural science and conduct research. "I was 17, studied natural sciences at high school in Reykjavik and took a course in physiology. I was fascinated and realized then that it was something along these lines that I wanted to do for a living. A lot of people suggested becoming a medical doctor, but I chose to study biology. Back then she was specially interested in nutrition. "I wanted to know why we eat, or rather, how food builds us, how our bodies grow from the small molecules that constitute food", she explains. The course she wanted to take was not available in Iceland and this was the reason for her first move abroad.
It took more than 20 years
In 2000 Bryndis Birnir arrived at Lund University where she collaborated with Professor Patrik Rorsman. Their common interest was GABA. He focused on GABA from the insulin-producing beta cell whilst she concentrated on the function of low levels of GABA in the brain and in the beta cells. It had taken more than 20 years but now GABAs role in the regulation of blood glucose levels was established as a scientific fact. "The scientific world is conservative. We ought to discuss novel findings more", she says.
Perhaps also applicable to type 1 diabetes
"Today it is all about learning more about GABA and trying to use the knowledge so that this neurotransmitter can have a role in the treatment of type 2 diabetes and many other diseases, perhaps even type 1 diabetes", notes Bryndis Birnir. "GABA that is secreted from beta cells can affect the T cells of the immune system, which also has ion channels for GABA, and because the hypothesis is that it is the T cells that kill the beta cells in type 1 diabetes there could be an association. We do not know what the connection is but that is what we are trying to find out".
Important when nerve cells are born
There is another way that GABA can be of interest in connection with type 1 diabetes. "We know that when a nerve cell is born, GABA is important for its development. The same can be true for beta cells and if that is the case it means that it is possible to encourage the new formation of these cells", says Bryndis Birnir and reveals that she is planning animal trials together with scientists from Uppsala and LUDC where GABA will be tested. The goal is to increase the formation of new cells and to protect the beta cells from autoimmune destructions.
Bryndis Birnir has been professor of neurosciences at Uppsala University since 2008. "I do not do much else apart from work. It is not possible to have another big interest apart from the research", she says, but mentions long-distance skating and rollerblading nonetheless. "I am very happy here in Uppsala, both professionally and geographically, and I am pleased with my life with GABA, it has been and still is very exciting. I am especially satisfied with the fact that I have been maintaining that GABA is important even at very low levels", she adds.
Text: Tord Ajanki/Camilla Franks
Picture: Dragan Paulovic, MalmöBild AB (Bryndis Birnir) och DreamStime