New Diabetes Gene Discovered

Finding could help most of those with type 2 diabetes, researchers say

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By
HealthDay Reporter

FRIDAY, Aug. 12, 2005 (HealthDay News) -- Scientists have discovered a gene that plays a role in the most common type of type 2 diabetes, and they say the discovery could pave the way to a targeted treatment.

Defects in the gene, called ARNT, caused mice to develop abnormalities in insulin secretion, the researchers report in the Aug, 12 issue of Cell.

"This gene, ARNT, is the first gene identified to be abnormal in the pancreatic islet cells, the cells that make insulin, in people with the common type of type 2 diabetes," said study leader Dr. C. Ronald Kahn, president and director of the Joslin Diabetes Center at Harvard Medical School.

"Type 2 diabetes is a mixture of diseases," Kahn said. "There are some rare types called maturity-onset diabetes of the young (MODY). For those types, only six genes cause it, and all got identified. For the remaining 95 percent plus of people who have the more common form, we don't know which genes cause the disease."

Kahn's team used DNA technology first to identify genes that were altered in their level of expression in islet cells, also called beta cells, isolated from people with type 2 diabetes. Next, they created a defect in one of these genes, called ARNT, in mice. The mice developed abnormalities in insulin secretion similar to that seen in people with type 2 diabetes.

The ARNT gene is crucial for normal development of the embryo, and also controls the expression and activity of many other genes.

"This gene was known to exist for quite a few years, but has mainly been studied in other tissues such as the liver, kidney and brain," Kahn said. "No one actually knew it was present in islet tissue."

In the study, Kahn's team found the expression of the gene in the islet cells of those with common type 2 had decreased by 80 percent to 90 percent. Then, they looked at whether the decreased expression affected the way islets make or secrete insulin in mice.

"What we showed is, if you lower the level of ARNT in beta cells, they will lose some of the ability to secrete insulin in response to a sugar challenge, similar to what you see in those with type 2 diabetes," Kahn explained.

Yet to be answered is why the level of expression of the ARNT gene is lower in those with diabetes, he added. Eventually, the hope is to find out how to boost the expression of the gene.

Dr. Robert Rizza, president of the American Diabetes Association, praised the research.

"By doing studies such at this, looking at genes that are active or not active, there have been a whole variety of genes now identified," he said. "And this is another one."

"It's very likely this disease is not going to be caused by a single gene," he said. "The common type of diabetes seems to be caused by multiple genes interacting."

"It's a very important finding," he said. "By altering one or two genes that play a role in the development of diabetes, you may be able to cure it."

More information

To learn more about diabetes, visit the American Diabetes Association.

SOURCES: C. Ronald Kahn, M.D, president and director, Joslin Diabetes Center, and the Mary K. Iacocca Professor of Medicine, Harvard Medical School, Boston; Robert Rizza, M.D, president, American Diabetes Association, and professor, medicine, Mayo Clinic College of Medicine, Rochester, Minn.; Aug. 12, 2005, Cell

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