Same protein plaque behind diabetes and neurological diseases

Helena Edlund is examining how insulin resistance can cause a protein to aggregate in key cells, thereby causing type 2 diabetes, Alzheimer’s or Parkinson’s disease.

Helena Edlund

Professor of Molecular Embryology

Wallenberg Scholar

Umeå University

Research field:
Pancreatic development

Edlund, who researches into diabetes, pops into the lab, where a colleague is in the process of cutting a mouse liver into thin slices. He is looking for signs of amyloid. Amyloid is an aggregation of proteins formed by misfolded variants of proteins that occur naturally in the body.

“We devote much of our energy to time-consuming work that we have to do to rule out various possibilities. I don’t think we’ll find amyloid in the liver – it would be astonishing if we did. That’s why being a researcher is so enjoyable. We can uncover things no one would have dreamed of,” Edlund enthuses.

Higher risk of dementia

Edlund and her research team at Umeå Center for Molecular Medicine (UCMM) are attempting to understand what triggers type 2 diabetes.

“Although we know quite a lot about the risk factors behind the onset of diabetes, there are still considerable gaps in our knowledge,” Edlund says.

Type 2 diabetes mainly affects older people and the overweight, since ageing and obesity can impair the body’s ability to respond to insulin – a condition known as insulin resistance.

Insulin is a hormone formed in beta cells in the islets of Langerhans in the pancreas. It is released into the bloodstream so that sugar in food can be absorbed by tissues and converted into energy. When insulin resistance occurs, more and more insulin is needed for the tissues to be able to absorb sugar, which in turn increases the pressure on the insulin-producing beta cells.

“We’re studying how insulin resistance impacts beta cells in particular, and especially how it leads to amyloid formation, or protein clumping, which in turn impairs beta cell function, and causes the onset of diabetes,” Edlund explains.

Similar processes take place in neurons in patients with Alzheimer’s and Parkinson’s. Both of these neurodegenerative diseases are linked to insulin resistance.

In type 2 diabetes the main protein that aggregates is Islet Amyloid Polypeptide (IAPP), which forms clumps that impact the beta cells. In Alzheimer’s, the protein that aggregates in neurons is amyloid beta. Alpha-synuclein forms clumps in the neurons of Parkinson’s sufferers. The correlation between insulin resistance and type 2 diabetes, Alzheimer’s and Parkinson’s disease may indicate that the mechanisms underlying the formation of amyloid are common to all three.

“Alpha-synuclein is also expressed in beta cells. We have shown elevated levels of alpha-synuclein in a genetically manipulated mouse model with impaired beta cell function, and in beta cells in type 2 diabetics,” Edlund says.

The link between diabetes and neurodegenerative disease is also confirmed by clinical data. Type 2 diabetics run a 65 percent higher risk of developing Alzheimer’s and a 36 percent higher risk of Parkinson’s.

Not tempted by postgraduate studies

Edlund began her studies on the chemistry program in 1979, but changed over to molecular biology after attending a lecture on DNA and molecular biology, which was a rapidly expanding research field at the time, particularly in Umeå.

“It was a real epiphany. There were five of us who changed program at the same time. We found it so fascinating.”

She had no plans to study for a PhD once she had graduated. It seemed both stressful and really hard work.

After two years or so at a research laboratory, she felt it was time to move on, but did not find a project that really attracted her until she heard about Thomas Edlund’s study on regulation of the insulin gene. Having received her PhD, she obtained a position as a research assistant, and put together her own research team.

Edlund has always been on the lookout for new methods of studying pancreatic development. Her team was one of the first in Sweden to make a “knockout mouse”. They inactivated (“knocked out”) a gene that regulates insulin production in beta cells. The result was a mouse without a pancreas.

“It was a real breakthrough. I never imagined that the gene was essential to the very formation of the pancreas.”

Daring to push the boundaries

In 2010 Edlund was chosen as a Wallenberg Scholar, a program supporting pre-eminent researchers at Swedish universities. In 2016 her grant was extended by a total of SEK 15 million over five years by Knut and Alice Wallenberg Foundation.

“It’s unique to be awarded research funding that is not linked to a specific project. I can commit to researching ideas I’ve been pondering over, and really give my all.”

For decades she has been studying how the pancreas is formed and works. In recent years she has become increasingly interested in the clinical aspects of diabetes and obesity.

“Overweight is one of the world’s major health problems. It carries with it a risk of neurodegenerative disease, and cardiovascular complications.”

She enjoys research most when she discovers the underlying reasons for a disease, and can attempt to find remedies. She and Thomas Edlund have started a company with the object of developing therapies for diseases arising as a result of diabetes.

For the moment she is pleased to have found a common denominator for a number of diseases linked to insulin resistance.

“I think we’ve found a new mechanism showing how amyloid is formed and spreads between insulin-producing cells, which may in turn be relevant to our understanding of how diabetes develops. It would be enormously interesting if the mechanisms also turn out to be a common factor in other diseases involving protein aggregation, such as Alzheimer’s and Parkinson’s. But we’re not there yet.”

Text Carin Mannberg-Zackari
Translation Maxwell Arding
Photo Magnus Bergström


More about Diabetes:

Diabetes is a disease that attacks the functions of the pancreas.

In type 1 diabetes the loss of beta cells prevents the pancreas from producing enough insulin.

In type 2 diabetes, the body’s cells have reduced sensitivity to insulin, which impairs the ability of insulin to stimulate absorption of sugar.

Nearly 400 million people in the world have diabetes. Projections suggest that number will have risen to 600 million by 2035.


More about Helena Edlund's research:

Poor cleaning impacts diabetes, obesity and neurodegenerative diseases