Researchers from Yale have identified the process by which inflammation can impair normal metabolism and lead to high blood sugar levels and the development of type 2 diabetes.

Insulin plays a double role in lowering blood glucose levels. The first method is well known, in that insulin helps glucose from the blood enter cells of the body for energy. The second method is that insulin helps to decrease the liver’s production of glucose. It is this method in which researchers hypothesized how insulin prevents glucose production by the liver.

Their hypothesis is that insulin suppresses the breakdown of white fat in the body which leads to a reduction in hepatic acetyl CoA and pyruvate carboxylase activity. The result of this is increased glucose production in the liver.

The Yale researchers then showed that inflammation within white fat also leads to increased glucose production by the liver when insulin resistance is present. The effect of insulin resistance was tested using rats and mice that had genetically impaired insulin signalling.

The most common type 2 diabetes drug, metformin, works by inhibiting glucose production by the liver but lead author of the study, Professor Gerald Shulman, notes that it does not achieve this by targeting the root cause. He states: “By understanding the molecular basis for hepatic insulin resistance we now can design better and more effective drugs for its treatment.”