Non-alcoholic fatty liver disease (NAFLD) is the term used for a range of conditions caused by an accumulation of fat in the liver. The predominant theory is that this condition is caused by insulin resistance, which is also the major factor in the development of type 2 diabetes mellitus. However, so far it was not clear if there is a causal association between these two conditions.
Recent studies by a Yale research team had found factors that disrupt the normal function of insulin in the liver. Now, the team headed by Gerald Shulman, Yale professor of medicine and investigator of the Howard Hughes Medical Institute, identified a direct association between NAFLD and changes in insulin and blood sugar that in turn cause type 2 diabetes.
The group of researchers found in rodent models of NAFLD a single amino acid in the insulin receptor that undergoes a process by which phosphate is added to an amino acid, called phosphorylation, causing liver insulin resistance.
“We were able to demonstrate the importance of this amino acid in causing liver insulin resistance associated with NAFLD by mutating this threonine amino acid to an alanine, which cannot undergo phosphorylation, and found that we could prevent hepatic insulin resistance despite the presence of fatty liver disease,” Shulman said.
This study, published in the Journal of Clinical Investigation, may open new lines of research to find a therapy for type 2 diabetes by targeting this original molecular cause of insulin resistance. This is particular relevant since practically all treatments for this disease focus on controlling blood glucose levels, but they not cure the insulin resistance.
Source: Yale News
