Possible Genetic 'Switches' for Blood Sugar Control Detected

TUESDAY Nov. 2, 2010 -- A new genetic analysis has uncovered specific regions in the DNA of certain human pancreatic cells that appear central to the regulation of insulin and other functions of the pancreas.

The new effort -- conducted by researchers at the National Human Genome Research Institute (NHGRI) -- takes scientists a step closer towards understanding the complex genetic underpinnings of insulin deficiency and the onset of type 2 diabetes, which accounts for most of the 23 million cases of diabetes among Americans and the more than 170 million cases worldwide.

By honing in on clusters of hormone-producing pancreatic cells known as islets, the investigators were able to detect about 18,000 "molecular on-off switches" (or so-called "promoters") that control gene behavior. Several hundred of these gene-adjacent switches were previously unknown.

In a U.S. National Institutes of Health (NIH) news release, study co-author Michael Stitzel explained that previous gene-mapping work has pointed out some genetic differences between type 2 diabetic and non-diabetic individuals in specific regions of the genome.

"But substantial efforts are required to understand how these differences contribute to disease," he said. "Defining regulatory elements in human islets is a critical first step to understanding the molecular and biological effects for some of the genetic variants statistically associated with type 2 diabetes."

Stitzel and colleagues from the NIH Intramural Sequencing Center, Duke University in Durham, N.C., and the University of Michigan in Ann Arbor report their findings in the Nov. 3 issue of Cell Metabolism.

The new work has also enabled the authors to identify another 34,000 regulatory "modules" located slightly farther away (than the 18,000 on-off switches) from the genes they control. They believe that these distinct "regulatory elements" may be critical to proper blood glucose levels.

Upwards of 50 genetic abnormalities believed to have an association with islet-related pancreatic dysfunction were also uncovered.

"These findings represent important strides that were not possible just five years ago, but that are now realized with advances in genome sequencing technologies," Dr. Eric D. Green, NHGRI director, noted in the NIH news release.

"Very exciting" is how Dr. Stuart Weiss, an endocrinologist at New York University Medical Center and a clinical assistant professor at the NYU School of Medicine in New York City, described the current effort.

"It's clearly the future of medicine," he said. "However, the fact of the matter is that all sorts of factors are involved in the development of diabetes, and different people require different treatments. And just when you think that you understand it, another curve comes at you. So it's very difficult to think that we're going to find a magic bullet. And I would think that the clinical applications from any of this are probably years and years away."

More information

For more on genetics and diabetes, visit the American Diabetes Association.

Posted: November 2010


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