Enzyme GAPDH found to regulate insulin pathways.

Rearchers at New York University and the Scripps Research Institute discovered that a previously known glycolytic enzyme, GAPDH, also actively regulates the insulin pathway. In addition, the team found that the inhibition of GAPDH attenuates the diabetic disease symptom in model animals. The scientists thus believe that the finding could add another target in addressing diabetes.

The research team screened hundreds of chemical compounds to find one hit compound, which rescued the model of C. elegans from diabetes. They identified the target protein to be the enzyme GAPDH. The hit compound was named GAPDS (GAPDH segregator) as GAPDS disassemble’s the multipart 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 treat diabetes.

Treating C. elegans with chemical compounds presented difficulties for the researchers because they grow on the surface of agar. To overcome these challenges, the researchers devised a soaking method in which the worms were placed in a compound solution for 24 hours. By this method, the worms were exposed to equitable concentration of the compounds and remained in a growth arrested state. The researchers added compounds and observed a regrowing of the worms into normal size by GAPDS, which is analogous to treating diabetes patients with a drug.

The research team, which included NYU’s Departments of Biology and Chemistry and Scripps’ Department of Cell Biology, reported their findings in the December 2006 issue of the Nature Chemical Biology journal.

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