Study identifies fat-secreted protein linked to insulin resistance

According to senior author Barbara B. Kahn, M.D., chief of the Division of Endocrinology, Diabetes, and Metabolism at BIDMC, these findings in mice and humans show that elevated levels of retinol-binding protein 4 (RBP4) contribute to insulin resistance, a primary risk factor for diabetes.

Produced by the pancreas, insulin helps cells take in glucose and convert the sugar to energy. In insulin-resistant individuals, the body’s cells cannot properly respond to the hormone, resulting in a build-up of glucose and insulin in the blood, which can lead to diabetes and cardiovascular disease.

Earlier work in Kahn’s lab had focused on the role of the glucose transporter protein GLUT4 in insulin resistance. Knowing that down-regulation of GLUT4 expression in fat tissue is an almost universal feature of insulin-resistant states, Kahn’s lab developed two transgenic mouse models: one with fat cell overexpression of GLUT4 and one with fat cell reduction of GLUT4. They found that the mice with overexpression of GLUT4 demonstrated enhanced glucose tolerance and insulin sensitivity, while the mice with reduced GLUT4 expression became insulin-resistant and had an increased risk of diabetes.

Kahn’s team then conducted a global microarray analysis to identify the protein RBP4 and found elevation of RBP4 can cause insulin resistance and that decrease of the protein in insulin- resistant states would ameliorate the condition.