Type 2 diabetes linked to a family of metabolic genes

BOSTON -- An ambitious and exhaustive genetic study, led by investigators at the Joslin Diabetes Center and the Children's Hospital Boston Informatics Program, has pinpointed a group of genes that are involved in type 2 diabetes and shows that the activity of these genes changes even before overt diabetes develops. The study appears in a July 2003 edition of the Proceedings of the National Academy of Sciences (1).

The investigators at Joslin, led by Dr. Mary-Elizabeth Patti, an endocrinologist and scientist and director of the Genomics Laboratory at Joslin, wanted to identify genes that might be altered in people with diabetes and in those at high risk for the development of diabetes. To do this, they used a microarray a small slide dotted with small pieces of DNA to simultaneously measure the activity of over 7,000 genes in muscle tissue from Mexican-Americans, an ethnic group with a very high risk for diabetes. They compared three groups: subjects with diabetes, healthy subjects without diabetes, and high-risk subjects with "prediabetes" (diabetes in family members).

"Knowing which genes are turned on or off in people before they develop diabetes is a key piece of information needed to solve the puzzle of diabetes, and to identify new ways to treat and prevent this devastating disease," Dr. Patti explains.

Two genes, PCG1-alpha and PCG1-beta, showed reduced activity (also known as expression) not only in the people with diabetes, but also in those with prediabetes. This decreased activity appeared to lead to reduced activity of a larger group of genes involved in the metabolism of fats and carbohydrates. These genes code for proteins in the mitochondria, cell structures that play a critical role in energy metabolism. Reduced activity or expression of these genes may tip the scales to insulin resistance, or an inability of the body's cells to use insulin properly -- the first metabolic defect on the road to type 2 diabetes.


Contact: Rachel Whitehouse
Joslin Diabetes Center

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