New molecule helps explain the causes of obesity-related type 2 diabetes

A newly-identified molecular mechanism could explain how inflammation triggers type 2 diabetes, according to new research.
The study, conducted by researchers from the Harvard T.H. Chan School of Public Health, suggests that addressing a connection between certain molecular processes could lead to improved treatments for type 2 diabetes.
Focusing on liver cells, the researchers found that the inflammation caused by obesity can increase the production of nitric oxide. Excessively high levels of nitric oxide are dangerous; they often impair the function of endoplasmic reticulum (ER) cells, which have an essential role to play in the regulation of glucose levels in the body.
Previous research has led to the assumption that ER impairment leads to inflammation, but this study suggests that things happen the other way around. Usually, the damage caused to the ER by inflammation is repaired by a process called the unfolded protein response (UPR). But in some cases the increased levels of nitric oxide triggered by obesity inflammation damage the UPR, so the ER is not repaired. Insulin resistance and type 2 diabetes occur as a result.
To test this theory, the researchers developed a version of the UPR that was immune to the effects of nitric oxide. They tested it on obese mice, and they found that the mice were protected against inflammation and insulin resistance.
It should be noted, however, that the findings are only relevant to cases of type 2 diabetes triggered by obesity, which is far from the only cause of type 2 diabetes. Other possible causes include Polycystic Ovary Syndrome (PCOS) and genetic factors.
The next step for the researchers it to test their findings on humans.
Senior author Gökhan S. Hotamisligil, JS Simmons Professor of Genetics and Metabolism and chair of the Department of Genetics and Complex Diseases and the Sabri Ülker Center at Harvard Chan School said: “These results establish that in an environment suffering from chronic inflammation, cellular organelles 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.”
The research was published in Science.