Glucagon Resistance: A Term that Nicolai is Helping Add to the Textbooks
Nicolai J. Wewer Albrechtsen, winner of the Danish Diabetes Academy’s Young Investigator Award 2021, is introducing a new biological concept to the world of research.
Insulin is a word familiar to more or less everyone in Denmark. As diabetes is such a common disease in this country, many people also know the term ‘insulin resistance’. But the word glucagon is one that is not yet familiar, and even less so the term ‘glucagon resistance’.
Young scientist Nicolai J. Wewer Albrechtsen wants to change that.
- Glucagon resistance is a completely new biological concept that will be part of medical training in the future, just as insulin resistance is today, he says.
And it affects a great many people. Nicolai Albrechtsen’s best estimate is that glucagon resistance is as prevalent as insulin resistance, which is found in about 30% of the world’s population. And this, he says, disproves something widely regarded as a fact: that glucagon is just a hormone that releases sugar from the liver when your blood sugar is low. In fact, glucagon does a lot more than merely control our blood sugar. For example, it plays a part in insulin secretion, protein metabolism and fat metabolism.
It is Nicolai Albrechtsen, his team and his Danish and international colleagues who are responsible for the new biological concept of glucagon resistance, and it is primarily his work on glucagon that has prompted the Danish Diabetes Academy to present him with this year’s Young Investigator Award.
Nicolai Albrechtsen is a doctor, researcher and associate professor working at the NNF Center for Protein Research, Faculty of Health and Medical Sciences, and the Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen. He is 33 years old and has just celebrated his tenth anniversary – and received some very generous gifts: not only this latest title of Young Investigator of the Year but also, earlier in the year, the Future Leaders Award from the European Foundation for the Study of Diabetes, the Sapere Aude award from the Independent Research Fund of Denmark (each worth DKK 5 million) and the Danish Diabetes Association’s Research Bursary, worth DKK 500,000.
It will be 100 years ago next year that glucagon was recognised as a hormone that helps the liver to release sugar so that a person’s blood sugar rises – in contrast to insulin, which reduces it. Glucagon comes from the pancreas every time we eat, and it helps the body to control our metabolism. Glucagon analogues are used to treat low blood sugar, but the possibility of using them to treat fatty liver (so-called dual agonists) is also being investigated.
Mentor: He is exceptionally talented
It was his former boss and current mentor, Professor Jens Juul Holst, who nominated him. Professor Holst describes Nicolai as ‘incredibly hard-working, exceptionally talented, smart and well-liked both in Denmark and abroad’, adding that, despite his youth, he has published over 130 articles, including more than 100 original, peer-reviewed scientific papers and 25 peer-reviewed reviews in international journals such as the important and well-known Cell Metabolism, Diabetes, Diabetologia and Nature Biotechnology. Very unusually for such a young researcher, he also has an H index (a measure of how often a researcher’s scientific studies are cited) higher than his age (an index of 34 in Nicolai’s case).
- These articles – and the work behind them – have increased our understanding of glucagon considerably, writes Jens Juul Holst in the nomination.
Never say ‘first in the world’
Nicolai Albrechtsen himself says that one of his PhD supervisors always maintained that you should never say that you are ‘the first in the world to find’ something, nor should you ever present your findings as ‘novel’ – ‘because there are a lot of us doing research all over the world’. Still, he will put his head just far enough over the parapet to say that he is very proud of his contribution to knowledge of glucagon and glucagon resistance.
For example, he believes that he and his colleagues have found the explanation for a link between diseases of the liver and diabetes: two cords like old-fashioned phone cables – a so-called feedback system – connecting the liver and the pancreas.
- When the liver gets sick, the pancreas is affected, and vice versa. If we cut the cables, it goes haywire. Then too much glucagon is produced, he says, explaining that the finding provides an understanding of the link between a fatty liver and the risk of getting diabetes.
- So, if we can reduce the fat in the liver, the risk of diabetes will be reduced, he says.
‘He disproves something widely regarded as a fact: that glucagon is just a hormone that releases sugar from the liver when your blood sugar is low. In fact, glucagon does a lot more than merely control our blood sugar. For example, it plays a part in insulin secretion, protein metabolism and fat metabolism.’
Drugs already exist for fatty liver, but they need to be better, says Nicolai, and the group’s to-do list for the years ahead includes both developing more effective medication and developing a test to measure glucagon resistance for use in ensuring that a drug treatment is effective.
- Large, generous grants have given us the opportunity to set up some experimental cell and animal studies and to investigate whether any findings can be transferred directly to patients with metabolic disease. Then, we intend to investigate whether that knowledge can be used to improve glucagon signalling pathways in people with fatty liver disease, says Nicolai J. Wewer Albrechtsen.
The next step
The next, really big step for Nicolai Albrechtsen is to find out what impact glucagon resistance has on the whole body, as opposed to on the liver alone.
Generally speaking, Nicolai anticipates that an increased effect of glucagon will make for a healthier body and a healthier physiology.
One result has already been achieved: the group has shown that a commonly used heart drug, known as entresto, improves the body’s metabolism and sugar processing, and that this is partly because the drug actually doubles the quantity of glucagon.
Thinking while pushing the pram – and while tobogganing
On his website, Nicolai Albrechtsen says that he has dedicated his life to his research. He says this despite the fact that Olga, Erik and his wife Charlotte are obviously far more important. But it can all be fitted in.
- I think while I am out with Olga in her pram, and I think while I am tobogganing with Erik in this time before he starts nursery. Life and science go on, after all, although I am on paternity leave, he says, adding that life is much easier for him now that he is collaborating with ‘a lot of smart students’ who do much of the hard work. They are the ones turning up at the hospital at 7 am and getting the day’s patient trial ready, or coming in for weeks on end to give the lab animals different types of medication in the morning and evening.
And his wife understands him (most of the time, he says): she is a human biologist, and they met in the lab when they were both in training.
- That is fortunate. I just cannot help thinking about research all the time, he says.
About the "DDA Young Investigator Award 2021"
The DDA’s Young Investigator Award 2021 is worth DKK 25,000 and is a great honour in the world of diabetes. It is given to a young researcher under 40 carrying out research on diabetes in Denmark who has demonstrated promising research and contributed substantially to the understanding and treatment of diabetes.
FACTS ABOUT NICOLAI ALBRECHTSEN
→ Read about the winner of the DDA-Funded Scientist Award 2021, Signe Schmidt
→ See previous Award winners
CONTACT FOR DANISH DIABETES ACADEMY:
Tore S. Christiansen, Managing Director
Phone: 29 64 67 64