The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

The protein that protects insulin-producing cells

Photograph of two diabetes researchers in the lab.
Anna Blom and Ben C King have discovered that C3 protein protects insulin-producing cells. Photo: Rebecca Rosberg

Much research on diabetes focuses on understanding what happens when the insulin-producing cells are destroyed. Researchers at Lund University have instead chosen to investigate what protects the insulin-producing cells. Their research shows that a protein of the immune system protects the insulin-producing cells from inflammation and death.

The study, published in PNAS, is an example of basic research that may contribute to new treatments for both forms of diabetes in the future.

Although there are many differences between type 1 diabetes and type 2 diabetes, there are also similarities, such as inflammation of the insulin-producing cells. Researchers at Lund University have studied a protein called C3, which plays a central role in the body’s immune system. The protein is secreted from cells and is found in large quantities in the blood. Previous studies by the same researchers have shown that C3 is also present inside cells and plays an important role there. Now, their latest study in PNAS shows that the protein C3 protects insulin-producing cells from damage and death when it is present inside the cells.

“Much research on diabetes focuses on trying to understand what happens when the insulin-producing cells are destroyed. We have chosen a different approach that aims to understand what protects the insulin-producing cells,” says Anna Blom, professor of protein chemistry at Lund University, who led the study.

It is already known that a protein called IL-1B can cause inflammation and damage to the insulin-producing cells. The new study now shows that it is intracellular C3 that protects the insulin-producing cells from being damaged by IL-1B (see fact box “What the researchers did”).

Can lead to new treatments

In the long term, the knowledge about C3 can be used to develop new treatments aimed at protecting the insulin-producing cells, such as stem cell therapies for treating type 1 diabetes and type 2 diabetes.

“An objective among many diabetes researchers is to create treatments where stem cells are taken from the patient and converted into insulin-producing cells, which are then transplanted back into the patient. To achieve this, it is important to understand what is needed for the insulin-producing cells to function well. If we can increase the production of intracellular C3 in these cells, it may help the cells survive longer so that the treatment can be more effective,” says Ben C King, associate professor of inflammation research at Lund University, and co-senior author of the study.

Paving the way for new research

Among researchers studying the immune system, there is no consensus on whether C3 plays a significant role inside our cells. Anna Blom hopes that the new study will pave the way for new research that can increase our knowledge about the significance of intracellular proteins in the development of diabetes and other diseases.

“It has long been known that C3 plays a crucial role for the immune system in the bloodstream where it helps white blood cells to engulf infectious microorganisms. Our new study shows that the protein plays a different role when it is located inside the cell. We hope to see similar studies by other research groups that either confirm or contradict our results,” says research group leader Anna Blom.
 

What the researchers did

  • The researchers cultivated insulin-producing cells from rats. Using the gene scissors CRISPR/Cas9, they created cells that either lacked C3 or only produced the intracellular form of the protein. They then found that cells without C3 were more susceptible to the harmful effects of IL-1B, while cells with C3 were protected.
  • Their experiments on mice showed that insulin-producing cells lacking C3 were at greater risk of damage and death, leading to faster development of diabetes-like conditions.
  • The researchers could also confirm previous findings that intracellular C3 is present in human insulin-producing cells and that levels increase in the presence of IL-1B, particularly in connection with diabetes. This is probably because the protein is trying to protect the insulin-producing cells.
  • The protective effect can be linked to a protein called FRK. Previous studies by the same research group have shown that C3 interacts with FRK, which is known to contribute to the destruction of insulin-producing cells. In the new study, the researchers conducted experiments that demonstrated that the harmful effect of IL-1B on insulin-producing cells is inhibited when FRK and C3 interact with each other. 

Contact

Portrait of Anna Blom. Photograph.

Anna Blom, Professor of protein chemistry at Lund University
+46 40 33 82 33
+46 70 415 06 82
anna [dot] blom [at] med [dot] lu [dot] se

Anna Blom’s profile on Lund University’s research portal

Link to the research group’s website (protein-chemistry.lu.se)
 

Photograph of Ben King.

Ben C King, Associate Professor of inflammation research at Lund University
+46 739 19 22 16  
+46 40 33 78 30
ben [dot] king [at] med [dot] lu [dot] se (ben[dot]king[at]med[dot]lu[dot]se)

Ben C King’s profile on Lund University’s research portal

 

Short facts about the study

Subject: Diabetes research, beta cell biology, intracellular C3
Research area: Basic research
Study design: Peer reviewed publication, quantitative study, researcher-initiated study, animal study (40 mice)
Experimental investigation: In vitro, in vivo

Link to the study (pnas.org)

 

Funding

Knut and Alice Wallenberg Foundation, Swedish Research Council, Diabetesfonden, Swedish
Foundation for Strategic Research, ALF funding, the Albert Påhlsson Foundation, Diabetes Wellness Sverige, Magnus Bergvall’s Foundation, the Crafoord Foundation, Wiberg foundation, Alfred Österlund’s Foundation, and the Bo and Kerstin Hjelt Diabetes Foundation.

A significant part of diabetes research at Lund University is conducted within EXODIAB, which is a strategic research area (SRA) in Sweden. The ambition is to develop new treatments and drugs that can prevent or cure diabetes.