Reversal of type 1 diabetes in mice may eventually help humans

June 15, 2014, University of Cincinnati Academic Health Center

Investigators at the University of Cincinnati (UC) have found a therapy that reverses new onset Type 1 diabetes in mouse models and may advance efforts in combating the disease among humans.

The study, led by William Ridgway, MD, was presented Saturday, June 14, 2014, at the American Diabetes Association's 74th Scientific Sessions in San Francisco.

Type 1 is usually diagnosed in children and young adults and affects about 5 percent of all people with diabetes, according to the American Diabetes Association. In Type 1 diabetes, the body does not produce sufficient insulin, which is central to glucose metabolism: without insulin, blood glucose rises.

There is no cure for Type 1 diabetes though it can be controlled with insulin therapy. Symptoms of the disease include frequent urination, excessive thirst and weight loss even though you are eating more.

Researchers say the incidence of Type 1 diabetes and autoimmunity in general has risen rapidly since the mid-20th century, possibly the result of under-stimulation of innate immune systems which trigger autoimmunity in children and . In Type 1 diabetes, autoimmunity causes the body's T-cells to attack its insulin-producing .

Previously, it has been reported that non-obese diabetic mice have defects in innate immune cells and that TLR4, a toll-like receptor, plays a protective role in preventing Type 1 diabetes.

Ridgway, Alice W. and Mark A. Brown Professor and Director of the division of immunology, allergy and rheumatology at UC, says his team of researchers used an agonistic monoclonal antibody, UT18, to boost the activity of TLR4 and reverse new onset diabetes in a high percentage of newly diabetic non-obese mice.

"We have shown that by using an antibody to stimulate a specific molecule in the innate we can reverse—with a high rate of success—new onset diabetes in mice that have already developed the symptoms of diabetes," says Ridgway. "The cause of this reversal is a preservation of the endocrine pancreatic beta cells that produce insulin. These cells are preserved from the autoimmune attack which is the hallmark of Type 1 diabetes."

The key to reversing Type 1 diabetes in mice, says Ridgway, is catching the disease at its onset, which is typically within a very short time window. The time frame would be longer in humans, but it is still a relatively short time from new onset to end-stage Type 1 diabetes, says Ridgway.

Ridgway says this approach differs from most in combating Type 1 diabetes because his team's therapies in mice do not directly interact with T-cells. He says treatment of autoimmunity has often been directed at suppressing an over-zealous by eliminating auto-reactive T-cells.

"We are targeting a different part of the immune system," says Ridgway. "There are two arms of the immune system. One is called the adaptive immune system and the other is the innate immune system. Basically the T-cells and B-cells are in your adaptive immune system and they respond to many different antigens. The innate system tends to have a stereotypical response. We are targeting a receptor that is found mostly on the cells, such as dendritic cells.

"This same molecular TLR4 pathway operates in humans in many similar ways; though there are some differences, it is possible this new pathway of targeting the immune system could be tested in humans," says Ridgway.

Additional study will be required, but the therapy may hold promise because one agonistic anti-TLR4 agent is already FDA approved and others are under development, says Ridgway.

Explore further: How rotavirus infection accelerates autoimmune diabetes in a mouse model

Related Stories

How rotavirus infection accelerates autoimmune diabetes in a mouse model

March 27, 2014
A combination of genetic predisposition and environmental factors is believed to cause autoimmune (type 1) diabetes. A study published on March 27th in PLOS Pathogens gets at the mechanisms by which rotavirus infection contributes ...

The role of the innate immune cells in the development of type 1 diabetes

December 19, 2012
Julien Diana and Yannick Simoni of the "Immune Mechanisms in Type 1 Diabetes," Inserm/Université Paris Descartes, directed by Agnès Lehuen, have just published the results of their work on type 1 diabetes in the Nature ...

Connexins: Providing protection to cells destroyed in Type 1 diabetes

November 7, 2011
Type 1 diabetes is a lifelong disease characterized by high levels of sugar (glucose) in the blood. It is caused by the patient's immune system attacking and destroying the cells in their pancreas that produce the hormone ...

Study identifies immune cells that promote growth of beta cells in type 1 diabetes

September 27, 2013
Joslin researchers have identified immune cells that promote growth of beta cells in type 1 diabetes. This study provides further evidence of a changed role for immune cells in type 1 diabetes pathology. The study appears ...

Antibody affinity is decisive in Type 1 diabetes in adults

March 11, 2014
Patients with LADA – a form of autoimmune type 1 diabetes in adulthood – can be distinguished from patients with non-autoimmune type 2 diabetes by means of the antibody reaction affinity to the enzyme glutamic acid decarboxylase ...

Recommended for you

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.