With the Knud Lundbeck Award, the Scandinavian Society for the Study of Diabetes recognizes a researcher who has substantially contributed to the progress of diabetes research, mainly through work conducted within the Nordic area. But diabetes was not Erik Renströms main interest from the start. Research on the central nervous system was much more his line of work.
When Erik Renström began his career as a cardiologist in the 1980s, diabetes care was poor and, in his view, rather boring. As a result of his great interest in mathematics and physics, his early research was about electrophysiology, or more specifically ion channels and electrical signals.
“Ion channels are like doors in the cell membrane which open and close to allow in ions of a certain type”, explained Erik Renström.
But like the heart and the nervous system, the insulin-producing beta cells are also governed by electrical signals, and after meeting a colleague conducting research in cardiac intensive care in Borås where Erik Renström was on call one night, he applied to his future supervisor Patrik Rorsman, who is today an internationally outstanding diabetes researcher. And that is the path he is on now.
Insulin is a blood sugar-regulating hormone produced by the beta cells in the pancreas. Insulin is secreted when you eat to allow the body’s cells to assimilate energy. Type 2 diabetes develops when the body does not produce or cannot use insulin for various reasons.
When Erik Renström began his research, it was known that the beta cells secreted insulin in two phases, the first for five to ten minutes and a subsequent second phase. Why this was, and what happened in the beta cells, no one knew.
Meanwhile the technical conditions for studying internal cell processes with a microscope had improved and it was suddenly possible to see how the insulin granules moved and behaved inside the cell.
“Contrary to what was thought, it looked like an anthill, even inside resting cells”, said Erik Renström.
Instead of only being able to count insulin granules as was previously the case, it was now also possible to start studying their movement patterns.
“This has given us a better understanding of the reactions taking place in the first and second phase and the transition between them”.
Erik Renström and his research team are focusing on what happens inside the beta cells. By mapping on a molecular level what happens when insulin secretion is insufficient, they are trying to identify the mechanisms behind the process.
Many patients with type 2 diabetes don’t in fact lack insulin; their beta cells are full of insulin granules but they are not secreted or are secreted in insufficient numbers. Through his research, Erik Renström has shown that this may be related to changes in the genome or to hitherto completely unknown mechanisms between the beta cells and the innate immune system.
One result of a research project which went on for many years was the discovery that carriers of a certain gene, adra2-a, have stressed insulin cells with a severely impaired capacity to secrete insulin.
“It was a heavy project in many ways; my doctoral student at the time, Anders Rosengren, and I were working in the dark for a long time”.
Using a strain of rats bred to lack the specific gene, they were finally able to go from routine work to asking very specific questions instead, which then led to conducting the same experiments in human cells and finally to a patient study.
Many years of hard work finally produced results. They had not only identified a risk gene, but they were also able to describe the molecular connection and account in detail for what leads to type 2 diabetes in the carriers of the specific gene.
And not only that. A deregistered drug, Yohimbin, blocked the receptors on the beta cells and normalised the secretion of insulin!
Due to its many side-effects, the drug must first be modified, but in the long term it could lead to a new treatment for type 2 diabetes. Unlike current medication, which stimulates the secretion of insulin in various ways, the new drug would attack the very cause of the disease.
Renström explains his successes with the fact that he has always sought out new, exciting environments with creative and fun people. This was a determining factor in his decision to move to Malmö after completing his PhD to work with Professor Leif Groop, who established the Lund University Diabetes Centre in 2006, now a world-leading diabetes research centre. Erik Renström was also deputy coordinator of the centre for several years before becoming coordinator for another major research collaboration between Lund University and Uppsala University.
Another example of successful cooperation in spite of obvious differences in areas of interest, which began with mutual admiration and a wish to work together, is a project Erik Renström started with Anna Blom, a prominent researcher interested in the immune system.
Erik’s focus is on what happens inside the beta cells, whereas Anna Blom’s interest lies in what happens outside the cells. But instead of seeing obstacles, they realised that they complemented one another.
Together, they started to study genes involved in the innate part of the immune system, which clears out old cells from the body or attacks viruses or bacteria. A certain type of these genes is expressed (active) in the liver where a large part of the clearing work takes place; to their surprise the same genes were also expressed inside the beta cells. The gene they studied, cd59, turned out to affect the beta cell’s secretion of insulin as well.
“This is really exciting”, said Erik Renström, adding that it raises more research issues.
Showing that things are connected in a different way to what was thought – i.e. what is written in the textbooks – is also a driving factor for Erik Renström in his work, and cd59 is a telling example of that.
“Since inflammation and activity in the innate immune system is very common with diabetes, it is not impossible that there is a connection. Exactly how this connection works we don’t yet know, but we may find out in the future”, he says.
Footnote: The prize, the Knut Lundbeck Award, will be handed out at a ceremony in connection with the annual meeting of the Scandinavian Society for the Study of Diabetes in Oslo on 26 April.
Contact: Erik Renström, erik [dot] renstrom [at] med [dot] lu [dot] se , tel: 070/5223398
