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Off to a flying start with the fifth cell

As a PhD student he made a significant discovery when he identified ghrelin cells in the pancreatic islands. Four hormone-producing cells were already known to exist in the islands, including the insulin cell. The ghrelin cell became the fifth such cell. "In the scientific world, the discovery of a new type of cell in a human organ is a big deal. So naturally this was an important find. Especially for a young PhD student", says Nils Wierup.

Today, he heads the Neuroendocrine cell biology research group at Lund University Diabetes Centre in Lund. The group’s work covers histological methods. Histology is often described as microscopic anatomy and was one of the methods used by Nils Wierup when he became the first person to see the ghrelin cells. "We identified a distinct group of cells. These cells didn’t resemble the other cells and we were able to show that they were different using an electron microscope", says Nils Wierup and adds that histology is a little like bird-watching. In his capacity as a histologist and keen bird-watcher he ought to know what he’s talking about, but nonetheless the metaphor requires an explanation: "It’s all about finding the detail in a muddle of colours and shapes. I’ve always been good at this, be it birds in a tree or structures in human tissue", he says.

Bird-watching and histology

The ghrelin cell is the third most common hormone-producing cell type in the pancreas. In adults, these cells make up approximately one percent of all the cells in the gland. In foetuses and newborns, this percentage is ten times as high. It was already common knowledge that ghrelin cells are present in the intestinal canal and in nerves in the brain where their hormone stimulates appetite, for example. The discovery that the cells are also present in the pancreas signalled the start of some intensive mapping. The question was what the hormone's role is in the pancreas.

"It’s important that we are familiar with all the players and understand how they interact with each other. Our mapping showed that the ghrelin hormone is important. It inhibits the secretion of insulin through a direct effect on the insulin-producing beta cells", explains Nils Wierup.

Complex systems

One explanation to why foetuses and newborns have so many more ghrelin cells than adults could be that the cells by inhibiting insulin secretion protect the foetus against excessive blood sugar levels. "The fascinating thing with biology is that humans are so ingeniously designed. We’re made up of various complex systems that either counteract or support each other, and other systems that take over if something fails. There are always new discoveries to make", says Nils Wierup. As an example of this complexity, he refers to various animal models that have been used in research where a gene is knocked out, i.e. knockout mice. Often, not much happens in such cases despite a gene being missing. Other systems take over and maintain biological functions.

The gherlin cells in the intestinal canal may explain why type 2 diabetics that undergo obesity-related surgery are often cured of diabetes within only a few days of surgery, a long time before they actually lose the weight. "Nothing is removed during the surgery but the anatomy changes so that the food goes directly to the small intestine, it bypasses all gherlin production, which means the hormone doesn’t inhibit insulin secretion", explains Nils Wierup.

Big research grant

He discovered gherlin cells in the pancreas in 2001, early on in his PhD, and for some time the finding got all the attention. "Yes, it was so exciting that we focused on this and put a lot of other things on hold for some time. It was mainly the task of investing another hormone, CART, which had to wait. Since early on, this work represented the main track in Nils Wierup’s research. The CART work received a major boost in August 2008 when he was awarded the Novo Nordisk Foundation Project of Excellence of five million Danish kronor over five years and was granted a research assistant position by Vetenskapsrådet. "This was extremely important, the best possible outcome. The money meant I could set up my own research group", comments Nils Wierup. Today the group consists of Nils Wierup, two PhD students, one researcher with a PhD qualification, two laboratory assistants and professor emeritus Frank Sundler. The LUDC scientists were the first in the world to show that CART is yet another player in the line-up of hormones that regulates insulin secretion. "Compared to ghrelin, CART has the opposite effect. Together with the intestinal hormone GLP-1, CART has a major stimulatory effect on insulin secretion", says Nils Wierup.

Dream gole

On its own, GLP-1 has the same effect as CART. This makes the hormone the starting point for the development of new drugs for type 2 diabetes. "Through animal models, we’ve been able to show that the stimulatory effect is even stronger in combination with CART, and finding a way to combine the two hormones in one drug for type 2 diabetes would be the dream outcome. In diabetes research, the importance of intestinal hormones has become clearer in the past few years. "This is logical. This is where the food ends up. That’s when the beta cells have to go to work to produce insulin to prevent the blood sugar from rising", says Nils Wierup.

A more personal goal of his is visiting Falsterbonäset with his bird binoculars, a thermos flask of hot chocolat, and his daughter, who is not yet one. "Call me a nerd, but I like birds. If I see a bird I need to know what type it is. On the whole, I like nature, fishing, sailing... When I was five I decided to become a marine biologist, but after visiting the biology institution at Lund University it was clear to me that I would become a molecular biologist".

Free time

"I have the dream job. I decide myself how to plan my day. Sure, I often work very long hours, rarely less than fifty hours a week. Perhaps I’m a bit too curious", he says and ponders that other’s often focus on one project at a time. "And I work on perhaps twenty. Besides, I like working with other scientists who don’t work in exactly the same specialist area as I do. It widens my perspective and I think that’s beneficial", he says and means that he is also pretty good at taking time off. He has time to do what he wants, and the main time consumer right now, and for a few years ahead, is naturally his daughter Hedda. "It’s a great experience, becoming a dad", he says.

The flying start to his research career with the gherlin cells was naturally a highlight and motivation for the future. But, it was also a little bit scary. "Yes, giving talks at the major scientific conferences was pretty scary", he admits. Since then Nils Wierup’s progress has been fast. He is not yet 34 years, he is a docent, and he has his own research group and more than 40 published scientific papers under his belt. It is no longer scary to give talks, even at the largest conferences.

If there is a sixth hormone-producing cell in the pancreas, it is not unlikely that it is Nils Wierup or one of his team members who identifies it first.

Text: Tord Ajanki/Camilla Franks

nils wierup

Nils Wierup

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00