Type 1 diabetes: Reprogramming liver cells may lead to new treatments

Researchers have discovered a way to reprogram mouse liver cells into precursor pancreatic cells by changing the expression of a single gene. They suggest that the finding is an important step toward showing that reprogramming liver cells might offer a way forward for the treatment of type 1 diabetes in humans.

The team - led by researchers from the Max Delbrück Center for Molecular Medicine in Berlin, Germany - reports the study in the journal Nature Communications.

Diabetes is a chronic disease that develops either when the body cannot make enough insulin, or when it cannot effectively use the insulin that it does make. Insulin is a hormone that regulates blood sugar, or glucose, and it helps to convert glucose from food into energy for cells.

Uncontrolled diabetes leads to high blood sugar, or hyperglycemia, which over time causes serious damage to many parts of the body, including the heart, blood vessels, nerves, eyes, and kidneys.

In the United States, an estimated 29.1 million people have diabetes, including 8.1 million who are undiagnosed.

The most common type of diabetes is type 2, in which the body cannot use insulin effectively. Type 1 diabetes, in which the body does not make enough insulin, accounts for around 5 percent of diabetes cases in adults.

The new study is likely to interest researchers developing treatments for type 1 diabetes. In people with type 1 diabetes, the immune system attacks the insulin-producing beta cells of the pancreas.

The advantages of using liver cells

Researchers in regenerative medicine are exploring ways to generate new populations of pancreatic beta cells as a possible avenue for the treatment of type 1 diabetes.

Fast facts about type 1 diabetes

  • Type 1 diabetes can develop at any age
  • However, it is usually diagnosed in children and young adults
  • People with type 1 diabetes must take insulin every day.

Learn more about type 1 diabetes

The new study concerns a method called cell reprogramming, in which it is possible to convert one type of cell into another type of cell, by tweaking genes.

An obvious source of cells for reprogramming into insulin-producing beta cells might be other types of cell in the pancreas.

In their study paper, the researchers mention other research that shows such pancreatic cells display a high degree of the necessary "cellular plasticity."

However, the researchers chose to focus on liver cells because, from a clinical perspective, they offer important advantages over pancreatic cells; for example, they are more accessible and abundant.

They also cite studies that have partially corrected hyperglycemia in diabetic mice by reprogramming liver cells into pancreatic beta cells.

The new study shows how just by changing the expression of a single gene called TGIF2, the team was able to coax mouse liver cells to take on a less specialized state and then stimulate them to develop into cells with pancreatic features.

TGIF2 regulates 'pancreas versus liver fate decision'

When the researchers transplanted the modified cells into diabetic mice, the animals' blood sugar levels improved, suggesting the cells were behaving in a way similar to pancreatic beta cells.

The researchers identified TGIF2 (Three-Amino-acid-Loop-Extension homeobox TG-interacting factor 2) by running gene expression profiling tests on immature liver and pancreas cells isolated from mouse embryos as the cells differentiated toward their particular cell fates.

They found that at a particular differentiation branchpoint, the expression of TGIF2 changes in opposite directions as the cells commit to either liver or pancreatic fates.

The authors note that their study shows that "TGIF2 is a developmental regulator of pancreas versus liver fate decision," and when expressed in adult mouse liver cells, it suppresses the transcription program for liver cells and induces a subset of pancreatic genes.

There is still a lot of work to do to investigate whether the results with mice translate to humans. The team has already started working on human liver cells.

"There are differences between mice and humans, which we still have to overcome. But we are well on the path to developing a 'proof of concept' for future therapies."

Senior author Dr. Francesca M. Spagnoli, Max Delbrück Center

Learn how type 1 diabetes kills some insulin-producing cells but not others.