Nav: Home

How to block type 1 diabetes

June 01, 2017

Researchers at The Jackson Laboratory, Cyteir Therapeutics and collaborating institutions have found a way to protect beta cells from destruction -- achieving a longtime, elusive goal that could lead to therapies preventing type 1 diabetes (T1D).

In healthy people, white blood cells make antibodies against pathogens or other invaders. In the pancreas, pancreatic beta cells produce insulin, the hormone that provides fuel to the body's cells by transporting glucose. Another type of white blood cells -- B cells or B lymphocytes -- plays a major role in activating the autoreactive T cells (T lymphocytes) that then destroy the pancreatic beta cells leading to type 1 diabetes.

These damaged cells fail to carry glucose into cells; instead glucose builds up in the blood and can damage nerves, blood vessels and organs unless insulin is administered.

"So there has been a lot of interest in the diabetes research community: If you can target those antigen-presenting B-cells, that could be potentially a very effective disease intervention," says JAX Professor David Serreze, Ph.D., lead author of a highlighted study published in the Journal of Immunology. "Our approach targets an appropriate population of the B cells among the white blood cells, resulting in inactivation of the cascade of autoimmunity against the insulin-producing pancreatic beta cells, and hence subsequently blocking diabetes development."

The researchers used a gene manipulation approach to identify a potential metabolic target that would eliminate the B cells that initiate the whole diabetes-inducing process.

They demonstrated that non-obese diabetic (NOD) mice treated with a specific (AID/RAD51) pathway inhibitor had larger populations of certain B cells that were capable of suppressing diabetogenic T cell responses, and greatly reduced T1D development, compared with untreated controls.

Serreze says the research team "borrowed a playbook" from a new approach to treating B-cell lymphomas. Study coauthor Kevin Mills pioneered the approach as a JAX investigator and then cofounded Cyteir Therapeutics to bring the cancer therapy to clinical trials.

In the process of antibody production, B cells turn on the gene known as activation-induced cytidine deaminase (AID), which acts as a sort of molecular scissors that cut the chromosomes within the B-cell. In some cancers this process goes wrong, with AID acting out of control and creating mutations and chromosome rearrangements that make the tumor more aggressive. Mills has identified molecules that block the DNA repair action in these tumors, causing the cancer cells to die.

"To combat T1D," Serreze says, "we're taking out this whole pathway to block autoreactive cells. But on the flip side, you may want to keep this pathway active if you want to keep antitumor immune responses in place.

"Ultimately," he says, "this approach could potentially be applicable to any autoimmune disease that has a B-cell component."
-end-
Jackson Laboratory Research Scientist Muneer Hasham, Ph.D., Postdoctoral Fellow Jeremy Racine, Ph.D., Research Assistant Jeremy J. Ratiu and Predoctoral Associate Qiming Wang were coauthors of the study, as were researchers at Virginia Polytechnic and State University in Blacksburg, Va., and the University of Florida in Gainesville, Fla.

The Jackson Laboratory is an independent, nonprofit biomedical research institution based in Bar Harbor, Maine, with a National Cancer Institute-designated Cancer Center, a facility in Sacramento, Calif., and a genomic medicine institute in Farmington, Conn. It employs 1,900 staff, and its mission is to discover precise genomic solutions for disease and empower the global biomedical community in the shared quest to improve human health.

Jackson Laboratory

Related Diabetes Articles:

The role of vitamin A in diabetes
There has been no known link between diabetes and vitamin A -- until now.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
Type 2 diabetes and obesity -- what do we really know?
Social and economic factors have led to a dramatic rise in type 2 diabetes and obesity around the world.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
More Diabetes News and Diabetes Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...