Researchers Pinpoint Cause of Insulin Resistance in DM1

Recent studies suggest that myotonic dystrophy arises from a defect in the way muscle cells handle RNA -- the critical intermediate between DNA (genes) and proteins. Now, researchers are unraveling the disease process even further, by showing how those RNA defects alter the production of a specific protein.

The most striking symptoms of myotonic dystrophy are muscle wasting and myotonia (muscle stiffness), but the disease also causes an array of other symptoms, including a mild form of diabetes called insulin resistance. The most common form of the disease, myotonic dystrophy type 1 (DM1), is caused by a mutation called a repeat expansion -- a "stutter" in the chemical letters that make up DNA and RNA. With the recent discovery that myotonic dystrophy type 2 (DM2) is caused by a similar mutation in a different gene, researchers have come to believe that the expanded RNAs create a "traffic jam" in cells, blocking their ability to convert RNA into essential proteins.

An MDA-funded team led by Thomas Cooper at Baylor College of Medicine in Houston reports solid proof of that idea. In the September issue of Nature Genetics, Cooper and his team show that the expanded RNAs underlying DM1 alter the production of an insulin receptor (a cell surface protein that enables cells to respond to insulin). The expanded RNAs somehow cause cells to switch from making a highly sensitive insulin receptor to a less sensitive version, leading to insulin resistance.

Efforts are under way to determine how the expanded RNAs lead to other symptoms of DM1 and DM2, including myotonia and cardiac arrhythmia. With a better understanding of the disease process, researchers hope to design effective treatments, such as drugs that could block the damaging effects of expanded RNA.