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New Diabetes Gene Discovered

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. "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.

"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."
Cell. Aug, 12, 2005

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DID YOU KNOW:
Lilly Drug ruboxistaurin for Diabetic Complications Shows Mixed Results: Eli Lilly said one of its experimental drugs ruboxistaurin proved effective against diabetic retinopathy, but failed in late-stage trials to alleviate symptoms of diabetic neuropathy. Lilly said ruboxistaurin reduced vision loss in a trial among patients with diabetic retinopathy. Based on the trial’s success, Lilly said it plans to seek U.S. marketing approval of the drug to treat the condition by late this year.Lilly said the drug failed in two other late-stage trials to improve symptoms of diabetic peripheral neuropathy. The company said there was no significant change in sensory symptoms among patients with nerve damage getting ruboxistaurin and those receiving placebos. However, Lilly is continuing with separate trials to determine if ruboxistaurin can actually slow the progression of nerve damage.
Lilly plans to sell the drug under the brand name Arxxant.

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