Researchers at New York University and the Scripps Research Institute have discovered a new enzyme, GAPDH, which regulates insulin pathwaysa finding that offers a new direction for the treatment of diabetes. The research is reported in the most recent issue of the journal Nature Chemical Biology.
The enzyme GAPDH was previously unknown to be a factor in the development of diabetes in humans. It has also been discovered that the inhibition of GAPDH attenuates the diabetic disease symptom in model animals.
The research team, which included NYUs Departments of Biology and Chemistry and Scripps Department of Cell Biology, used the worm Caenorhabditis elegans (C. elegans) to identify a new therapeutic target protein for diabetic treatment. C. elegans is the first animal species where RNA interference (RNAi) is discovered and thus, an excellent model organism for chemical genetic research. In this study, the researchers screened hundreds of chemical compounds to find one hit compound, which rescues the mutant C. elegans (diabetics model) from diabetes. Then, they identified the target protein, which was found to be the enzyme GAPDH. GAPDH has long been known as one of the important glycolytic enzymes, and its function is affected by insulin. However, this is the first discovery that GAPDH actively regulates the insulin pathway.
The research team constructed all the molecules by incorporating the fishing tag (linker) from the beginning, and facilitated the target fishing. The hit compound was named GAPDS (GAPDH segregator) as GAPDS disassemble the multi-part structure of GAPDH into monomers. The segregation of GAPDH releases the suppressor of insulin signaling from the cell membrane, and thus activates the insulin signaling to eventually help to treat diabetes.
While the C-elegans is a recommended model for chemical genetic study, treating them with chemical compounds presented difficulties for the researchers because they grow on t
Contact: James Devitt
New York University