| Scientists at Johns Hopkins have uncovered a surprising and novel way of lowering blood sugar levels in mice by manipulating the release of sugar by liver cells. The results, published in the June issue of Cell Metabolism, have implications for treating conditions like diabetes.
The discovery by researchers in Johns Hopkins' Institute of Basic Biomedical Sciences and McKusick-Nathans Institute for Genetic Medicine reveals that a protein called GCN5 is critical for controlling a domino-like cascade of molecular events that lead to the release of sugar from liver cells into the bloodstream. Understanding the role of GCN5 in maintaining blood sugar levels is leading to a clearer picture of how the body uses sugar and other nutrients to make, store and spend energy.
The inability to properly regulate blood sugar levels leads to conditions like obesity and diabetes. Both type 1 and type 2 diabetes cause blood sugar levels to stay too high, which can lead to complications like blindness, kidney failure and nerve damage.
"Diabetes is a really big problem, even when patients are given insulin and stay on strict diets," says Carles Lerin, Ph.D., a postdoctoral fellow in cell biology at Johns Hopkins and an author of the report. "In the absence of a cure for the disease, we are really trying to focus on finding better treatment because currently available methods just don't work that efficiently," he says.
The body keeps blood sugar - known as glucose - within a narrow range. Extra glucose floating through the bloodstream, which is common after eating a meal, is captured and kept in the liver. When blood glucose runs low, the liver releases its stores back into the bloodstream. When those reserves are tapped out, liver cells turn on genes to make more glucose to fuel the body.
When the researchers put GCN5 into live mice, they found that it can in fact decrease blood glucose levels. Liver cells in mice that were given no food for 16 hours actively release glucose into the bloodstream. Introducing GCN5 into their livers, however, causes blood glucose levels in these mice to be reduced.
"These results show that changing GCN5 is sufficient to control the sugar balance in mice," says Puigserver. "Therefore, GCN5 has the potential to be a target for therapeutic drug design in the future." Go Back | 
