MAR 31, 2020 12:23 PM PDT

A Genetic Edit Shields Cells That Are Usually Destroyed by Type 1 Diabetes

WRITTEN BY: Carmen Leitch

Diabetes is a disorder in which the body cannot properly regulate blood sugar levels because of a problem with insulin, a hormone that enables the body to get sugar out of the blood and move it into cells. In type 2 diabetes, the body either doesn't make enough insulin or doesn't respond to it properly, and is thought to be due to a combination of genetic and environmental factors. Type 1 diabetes, however, is a disease in which the immune system attacks the cells in the pancreas that produce insulin. Those with the disorder completely lack insulin, and they have to carefully manage their blood sugar for their entire lives. It can lead to other health problems including heart disease and may shorten life expectancy by over a decade.

Cells in the pancreas of a gene-edited mouse produce nearly equal amounts of the hormones insulin (green) and glucagon (red). In mice that develop Type 1 diabetes, green would predominate, and insulin production would draw the deadly attention of a disordered immune system. / Credit: Courtesy of Hugo Lee

Researchers have now found that by removing a gene called IRE1-alpha from cells that produce insulin, called beta cells, in a mouse model of type 1 diabetes, the immune system stops attacking these cells. That relieves the symptoms of the disease because the cells can start producing insulin again. The findings, which have been reported in Cell Metabolism, suggest that it may be also possible to prevent other diseases in which the immune system mistakenly attacks the body's cells.

"The thing is, individuals who are at high risk can be identified," noted the lead author of the report, Feyza Engin, a biomolecular chemistry professor at the University of Wisconsin-Madison. "They have autoantibodies in their blood serum, meaning we can actually tell who is going to develop type 1 diabetes within a couple of years. But there's not much for clinicians to do but send them home, because there's no cure for type 1 diabetes."

The IRE1-alpha gene plays a role in how the cell responds to stress. The researchers expected that deleting this gene from beta cells in their type 1 diabetes mouse model would accelerate the progression of the disease. They were surprised to find something else happening.

"We expected the beta cells would die soon," Engin said. "Instead, my students told me that the blood glucose levels of the mice were becoming normal following an initial increase lasting a couple of weeks. I couldn't believe it. I said, 'What? No. Just measure it one more time.'"

Instead of being destroyed by the immune system's T cells, the beta cells were making insulin as they should normally. They were also becoming a bit less mature. If this so-called de-differentiation occurs before the T cells launch an attack, the interaction between the cells changes.

"Once we remove this gene, it's almost like the beta cells are undergoing a disguise," explained Engin. "They lose their mature identity. They de-differentiate and exhibit features of progenitor cells, and express hormones of other cell types in addition to insulin. When they de-differentiate, they don't act like typical beta cells anymore. They reduce the expression of many genes that signal to immune cells, 'Come and eat me!' Those signals go down, and that actually is altering the diabetogenic activity of T cells. They don't really recognize the beta cells as a problem anymore. They don't attack."

Importantly, the researchers found that the immature beta cells begin to mature again into totally functional beta cells.

"The mice experienced a little transient hyperglycemia. They have relatively high blood sugar, which isn't dangerous, for a few weeks," added Engin. "But then the beta cells get back to work, and make insulin like they're supposed to."

The scientists have continued to follow their mouse model, and have found that the T cells don't attack the beta cells again.

"That's the beauty of it," Engin said. "Even after the beta cells come back, the T cells leave them alone. They still have no diabetogenic activity one year later, which is like 40 or 50 years in a human life."

This research can now help scientists develop drugs that exploit this mechanism.

Sources: AAAS/Eurekalert! via University of Wisconsin-Madison, Cell Metabolism

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
SEP 27, 2020
Cell & Molecular Biology
How Spiders May Open a Path to IBS Treatment
SEP 27, 2020
How Spiders May Open a Path to IBS Treatment
Irritable bowel syndrome (IBS) is term that describes a gut disorder that causes abdominal pain, cramping, diarrhea or c ...
OCT 09, 2020
Cell & Molecular Biology
Proteins Have an Orientation in Plant Cells
OCT 09, 2020
Proteins Have an Orientation in Plant Cells
Just like animals, plants are made of cells that are full of proteins. The proteins in plant cells are often only found ...
OCT 13, 2020
Immunology
Why Halloween Is Extra Scary for Kids With Peanut Allergies
OCT 13, 2020
Why Halloween Is Extra Scary for Kids With Peanut Allergies
A recent study showed that there is an 85 percent spike in peanut allergy anaphylaxis cases on Halloween. The study, per ...
OCT 12, 2020
Cell & Molecular Biology
The Human Arm Appears to be Evolving Slightly
OCT 12, 2020
The Human Arm Appears to be Evolving Slightly
There are no humans that can perform feats of super-strength or control objects with their mind, but people are apparent ...
OCT 29, 2020
Genetics & Genomics
Severe Genomic Damage in Human Embryos Treated With CRISPR
OCT 29, 2020
Severe Genomic Damage in Human Embryos Treated With CRISPR
The CRISPR-Cas9 genomic editing system holds great promise for treating genetic errors that cause human disease. But we ...
NOV 14, 2020
Space & Astronomy
Bacteria Make Space Mining 400% More Effective
NOV 14, 2020
Bacteria Make Space Mining 400% More Effective
Researchers aboard the International Space Station (ISS) have shown that bacteria can increase space mining efficiency b ...
Loading Comments...