A once unnoticed molecular connection may show why obesity is a precursor to type 2 diabetes, according to a recent study published in the journal Science. Endoplasmic reticulum (ER) is integral in the balancing of glucose throughout the liver and other organs. However, researchers showed that when that balance is interfered with by nitric oxide, it can lead to obesity-related inflammation that has an adverse effect on ER. That effect will of course lead to impaired glucose levels, and possibly resulting in type 2 diabetes.
The inflammation starts the sequence of events which is then followed by increased nitric oxide production. The increased production leads to failure of the unfolded protein response, which relieves ER stress and restores function. With this failure, insulin resistance is caused and ultimately type 2 diabetes.
“These results establish that in an environment suffering from chronic inflammation, cellular organelles (ER) lose their vitality through a specific link that is identified in our study, and suggest that therapies that target inflammatory pathways, including nitric oxide production, could be effective strategies in the treatment of metabolic disease,” says senior author Gokhan S. Hotamisligil, JS Simmons Professor of Genetics and Metabolism and chair of the Department of Genetics and Complex Diseases and the Sabri Ulker Center at Harvard Chan School.