News & Research

By: Felicia Breedy

In a March 3, 2009 Reuters Health article, Gerald Shulman, MD, PhD, an ADA Distinguished Clinical Scientist Award recipient, was highlighted for his work related to the molecular mechanisms that are responsible for insulin resistance and type 2 diabetes. Dr. Shulman conducted his research at Yale University School of Medicine and found that a specific gene, PGC-1, appears to play a role in the development of insulin resistance in response to a high-fructose diet.

The addition of high-fructose corn syrup to foods has been proposed to be linked to the increased incidence of obesity and diabetes in the US. Previous studies have shown that the use of this sweetener in sodas and processed foods is potentially harmful because it is metabolized differently than glucose, and more readily converted to fat. Other studies have shown an increased risk of developing high triglyceride levels and fat buildup in the liver.

Dr. Shulman and his research team focused on the PGC-1 beta gene because of its action in the pathway that regulates the production of hepatic fat. Using rats in two diet groups, high starch versus high fructose, they blocked PGC-1 gene activity in the high-fructose diet group and found that the animals not only did not develop insulin resistance, but also failed to exhibit elevated triglyceride levels. Significantly, this data supports the theory that the PGC-1 beta gene plays an important role in fat buildup in the liver and inhibiting the gene’s activity could be a potential target for future treatments of this condition.

The original article can be found in the March 4, 2009 issue of Cell Metabolism.

(Nagai Y, Yonemitsu S, Erion DM, Iwasaki T, Stark R, Weismann D, Dong J, Zhang D, Jurczak MJ, Löffler MG, Cresswell J, Yu XX, Murray SF, Bhanot S, Monia BP, Bogan JS, Samuel V, Shulman GI. The role of peroxisome proliferator-activated receptor gamma coactivator-1 beta in the pathogenesis of fructose-induced insulin resistance. Cell Metabolism. 2009 Mar; 9(3):252-64.)