The Path to Diabetes

Researchers identify target for new diabetes therapies

(RxWiki News) By studying people who are at risk of developing diabetes, researchers at the Joslin Diabetes Center have identified a molecular pathway for new drug treatments.

Fully developed type 2 diabetes causes drastic changes to a patient's metabolism. Once these changes occur, it can become very difficult for scientists to identify the root causes of the disease because of so many intermingling factors.

In order to find what factors might enable the disease of diabetes, Dr. Allison Goldfine and colleagues examined small samples of muscle from three different categories of people across the spectrum of diabetes. Individuals in the first group were healthy and did not have diabetes or pre-diabetes. Those in the second group were at-risk of developing diabetes bacause they had a family history of diabetes and showed signs of insulin resistance, yet they still had healthy blood sugar levels. Those in the third group had fully developed type 2 diabetes.

The researchers found that a gene known as STARS was expressed (aka showing up) more than twice as much in at-risk and diabetic individuals than in healthy individuals. STARS triggers a reaction in another gene called SRF, as well as a group of genes regulated by SRF and a co-activator protein known as MKL1. This genetic pathway was expressed most in the cells of people with type 2 diabetes.

In order to verify their results, the researchers repeated the tests on cells cultivated in vitro, as well as on the muscles of insulin-resistant mice. They observed similar increases in expression of those same genes.

To distinguish if this molecular pathway contributed to insulin resistance, or if it was just coincidentally appearing at the same time, Dr. Goldfine and colleagues suppressed the expression of STARS in muscle cells from rodents, and found that glucose uptake increased in those cells. This meant that the expression of STARS was in fact playing a crucial role in the development of type 2 diabetes.

According to Mary-Elizabeth Patti, M.D., from the Joslin Diabetes Center, the discovery of this genetic pathway may provide scientists with a target for new diabetes treatments. What's more, she adds, it gives us a better understanding of how diabetes develops.

Diabetes affects an estimated 25.8 million children and adults in the United States. About 79 million Americans have pre-diabetes, putting them at high risk of developing full-blown diabetes.

This study, which was funded by the National Institutes of Health and the Graetz Fund, appears online in the Journal of Clinical Investigation.

Review Date: 
February 15, 2011