Identifying RBP4's less benign function as an instigator of insulin resistance may lead doctors towards new drug interventions that focus on limiting secretion of the protein among obese patients at risk for type 2 diabetes.

"We have found a molecule not previously known to have any role in insulin action and demonstrated that this protein can contribute to the development of diabetes by blocking the action of insulin," said study co-author Dr. Barbara B. Kahn, chief of the division of endocrinology, diabetes, and metabolism at Beth Israel Deaconess Medical Center in Boston.

Type 2 diabetes develops as the result of insulin resistance, a condition defined by the body's inability to properly utilize naturally produced insulin for the breakdown of sugars, starch and other glucose-rich foods into energy. The resulting dangerous buildup of glucose and insulin in the blood is also associated with a high risk for cardiovascular disease.

Noting that insulin resistance seems to go hand-in-hand with reduced levels of the glucose transporter protein, the researchers used specially bred mice to look for a causal relationship between levels of RBP4 and other fat-cell proteins. After eliminating a range of alternate molecular options, they observed that levels of glucose-carrying proteins fell as fat cell RBP4 production rose.
Further tests in both mice and humans confirmed that excess production of RBP4 appears to promote a drop in the glucose-carrying proteins. Insulin resistance, they concluded, might therefore be avoided if RBP4 levels could be reduced and controlled. Kahn's team reported the findings in the July 21 issue of Nature.