Study identifies mechanism that leads to diabetes, blindness

September 17, 2012
Insulin-secreting beta cells in the pancreas cannot make enough cyclic AMP in patients with Wolfram syndrome. As a result, the pancreas produces and secretes less insulin, and the cells eventually die. Credit: Urano lab

The rare disorder Wolfram syndrome is caused by mutations in a single gene, but its effects on the body are far reaching. The disease leads to diabetes, hearing and vision loss, nerve cell damage that causes motor difficulties, and early death.

Now, researchers at Washington University School of Medicine in St. Louis, the Joslin Diabetes Center in Boston and the Novartis Institutes for BioMedical Research report that they have identified a mechanism related to mutations in the WFS1 gene that affects insulin-secreting beta cells. The finding will aid in the understanding of Wolfram syndrome and also may be important in the treatment of milder forms of diabetes and other disorders.

The study is published online in the journal .

"We found something we didn't expect," says researcher Fumihiko Urano, MD, PhD, associate professor of medicine in Washington University's Division of Endocrinology, Metabolism and Lipid Research. "The study showed that the WFS1 gene is crucial to producing a key molecule involved in controlling the metabolic activities of individual cells." That molecule is called cyclic AMP (cyclic ).

The video will load shortly.
Researchers at Washington University School of Medicine in St. Louis and elsewhere have identified a cellular mechanism that allows a single gene to cause damage in many different systems in the body in patients with the severe form of insulin-dependent diabetes known as Wolfram Syndrome. Credit: Washington University BioMed Radio

In insulin-secreting beta cells in the pancreas, for example, cyclic AMP rises in response to , causing those cells to produce and secrete insulin.

"I would compare cyclic AMP to money," Urano says. "You can't just take something you make to the store and use it to buy food. First, you have to convert it into money. Then, you use the money to buy food. In the body, external signals stimulate a cell to make cyclic AMP, and then the cyclic AMP, like money, can 'buy' insulin or whatever else may be needed."

The reason patients with Wolfram syndrome experience so many problems, he says, is because mutations in the WFS1 gene interfere with cyclic AMP production in beta cells in the .

"In patients with Wolfram syndrome, there is no available WFS1 protein, and that protein is key in cyclic AMP production," he explains. "Then, because levels of cyclic AMP are low in insulin-secreting , those cells produce and secrete less insulin. And in nerve cells, less cyclic AMP can lead to nerve cell dysfunction and death."

By finding that cyclic AMP production is affected by mutations in the WFS1 gene, researchers now have a potential target for understanding and treating Wolfram syndrome.

"I don't know whether we can find a way to control cyclic AMP production in specific tissues," he says. "But if that's possible, it could help a great deal."

Meanwhile, although Wolfram syndrome is rare, affecting about 1 in 500,000 people, Urano says the findings also may be important to more common disorders.

"It's likely this mechanism is related to diseases such as type 2 diabetes," he says. "If a complete absence of the WFS1 protein causes , perhaps a partial impairment leads to something milder, like diabetes."

Explore further: Treatment target for diabetes, Wolfram syndrome

Related Stories

Treatment target for diabetes, Wolfram syndrome

August 7, 2012
Inflammation and cell stress play important roles in the death of insulin-secreting cells and are major factors in diabetes. Cell stress also plays a role in Wolfram syndrome, a rare, genetic disorder that afflicts children ...

Brain abnormalities seen in children with severe form of diabetes

July 12, 2012
(Medical Xpress) -- Children with a rare syndrome that includes a form of insulin-dependent diabetes have brain abnormalities that appear to set the stage for cognitive problems later in life, according to new research at ...

Researchers reveal crucial immune fighter role of the STING protein

June 18, 2012
Researchers at Weill Cornell Medical College have unlocked the structure of a key protein that, when sensing certain viruses and bacteria, triggers the body's immediate immune response.

Recommended for you

Link between cells associated with aging and bone loss

August 21, 2017
Mayo Clinic researchers have reported a causal link between senescent cells - the cells associated with aging and age-related disease - and bone loss in mice. Targeting these cells led to an increase in bone mass and strength. ...

Are stem cells the link between bacteria and cancer?

August 17, 2017
Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, ...

Two-step process leads to cell immortalization and cancer

August 17, 2017
A mutation that helps make cells immortal is critical to the development of a tumor, but new research at the University of California, Berkeley suggests that becoming immortal is a more complicated process than originally ...

New Pathology Atlas maps genes in cancer to accelerate progress in personalized medicine

August 17, 2017
A new Pathology Atlas is launched today with an analysis of all human genes in all major cancers showing the consequence of their corresponding protein levels for overall patient survival. The difference in expression patterns ...

Female mouse embryos actively remove male reproductive systems

August 17, 2017
A protein called COUP-TFII determines whether a mouse embryo develops a male reproductive tract, according to researchers at the National Institutes of Health and their colleagues at Baylor College of Medicine, Houston. The ...

New technique overcomes genetic cause of infertility

August 17, 2017
Scientists have created healthy offspring from genetically infertile male mice, offering a potential new approach to tackling a common genetic cause of human infertility.

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.