July 2023 

Dr. Julien Sebag is leading one of the research projects funded through the Bridge to Cure program. This month, his project has reached a major milestone, having been published in a prestigious journal. In this publication Dr. Sebag recognized the support provided by the FOE through the Bridge to the Cure program.

This publication is notable because in it Dr. Sebag and his colleagues report for the first a new approach to treat diabetes. The new approach uses a molecule they designed that activates a protein called GLUT4 that removes glucose from the blood stream in response to insulin. Under normal conditions, GLUT4 transport glucose from the blood to tissues such as skeletal muscle and adipose tissue where it is utilized or stored. The GLUT4 activation process is impaired in type 2 diabetes leading to high levels of glucose in the blood. Dr. Sebag reasoned that restoring the activation of GLUT4 should lower blood glucose and protect from type 2 diabetes. To achieve this, he developed a novel high throughput assay that allowed him to screen 50,000 molecules to identify those that can restore GLUT4 activation. In addition, he generated a new mouse model that enables measurement of GLUT4 activation in live animals. Using these brand new tools, Dr. Sebag identified an example molecule that improved the activation of GLUT4 by insulin and promoted glucose removal from the blood. He then synthesized several new molecules based on the example molecule, finding ones that are even more potent at restoring GLUT4 activation. When given to a mouse model of type 2 diabetes, these new molecules significantly improved the ability of those animals to maintain normal blood glucose. Importantly, he identified the target of the new molecules as the protein called Unc119b. This protein has not previously been implicated in the control of glucose homeostasis and this represent a new potential target for the development of anti-diabetic drugs. Ultimately, Dr. Sebag’s study represents a significant advance in the diabetes field since it identifies a new mechanism and new molecules to improve glucose abnormalities in type 2 diabetes. Ongoing work in Dr. Sebag’s lab is aimed at moving these results to humans by testing the safety and efficacy of these new molecules to treat diabetes in people.