Immune system discovery may lead to preventive therapy for diabetes

November 12, 2001

BOSTON - By manipulating a cell that controls the immune system's response to infections, researchers at Dana-Farber Cancer Institute and their colleague have prevented the onset of diabetes in mice predisposed to the disease. The finding one day may lead to the development of a preventive therapy for people at risk for type 1 diabetes.

The investigators report in the Nov. 20 issue of the Proceedings of the National Academy of Sciences that they were able to protect diabetes-prone mice from developing the disease by activating immune system cells known as iNKT cells. When they dismantled the "go" signal for producing these cells, the animals' diabetes worsened.

"As the mice progress in their disease, the number of these cells decreases," says the study's senior author, Brian Wilson, MD, PhD, of Dana-Farber. "Mice that are resistant to diabetes, by contrast, continue to accumulate the cells in their pancreatic tissue.

"Because iNKT cells work in much the same way in mice and humans, techniques for increasing the production of these cells could be the basis of preventive treatments for people with a genetic risk of diabetes."

The job of iNKT cells is to regulate the immune system's response to infections and other disorders, ensuring that only diseased tissue, not healthy tissue, is targeted for attack. Type I diabetes, an "autoimmune" disorder, occurs when the immune system mistakenly attacks healthy insulin-producing cells in the pancreas. The loss of insulin impairs the body's ability to utilize sugar, leading to a host of health problems including kidney damage, nerve damage, and loss of vision.

Scientists have known that a loss of iNKT cells causes diabetes to worsen in non-obese diabetic (NOD) female mice, which have an inborn tendency to develop the disease. The falloff in the number of the cells apparently weakens the immune system's ability to rein in an errant attack on the pancreas.

The new study involves a closer look at the body's mechanism for activating iNKT cells. The mechanism involves a class of cells known as dendritic cells, whose role is to alert the rest of the immune system to the presence of infection or another health problem. The surface of dendritic cells is studded with proteins called CD1d, which display lipids, or fat, molecules. One such potent activating lipid is known as alpha-galactosylceramide. When iNKT cells sense the presence of these molecules, the cells are activated, reining in the immune system's attack on normal tissue.

In the new study, Wilson and his colleagues administered alpha-galactosylceramide to NOD female mice to see if it would prevent them from developing diabetes. "It did, potently," says Wilson, who is also on staff at Massachusetts General Hospital and an assistant professor of medicine at Harvard Medical School. In the second part of the study, investigators silenced the gene for CD1d, preventing dendritic cells from displaying alpha-galactosylceramide on their surface. The result was that iNKT cells were not activated and the mice, which had a pre-diabetic condition, went on to develop full-blown diabetes.

In mice and people with pre-diabetic conditions, the normal interactions between dendritic cells and iNKT cells do not occur properly, leaving them more likely to get diabetes. The findings of the Dana-Farber study suggest that such individuals could be helped by increasing their supply of iNKT cells, perhaps by administering alpha-galactosylceramide to them.

"The success of our work in mice lays the groundwork for a clinical trial of this therapy in people at high risk for diabetes," Wilson says. "Preventing pre-diabetic conditions from progressing would be an important benefit to about one in 500 people in the U.S."
The paper's other authors are Yuri Naumov, Rudolph Gausling and Jack Strominger, Dana-Farber; Keith Bahjat and Michael Clare-Salzer, College of Medicine, University of Florida, Gainesville; Roshini Abraham, Mayo Clinic, Rochester, Minn.; Mark Exley and Steven Balk, Beth Israel Deaconess Medical Center, Boston; and Yasuhiko Koezuka, Kirin Brewery, Gunma, Japan.

The study was supported by the National Institutes of Health and the Juvenile Diabetes Research Foundation International.

Dana-Farber Cancer Institute ( is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), a designated comprehensive cancer center by the National Cancer Institute.

Dana-Farber Cancer Institute

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to