Insulin and insulin-like growth factor have an essential role in growth, development and the maintenance of metabolic homeostasis, including glucose uptake from the bloodstream. Researchers have identified mutations in insulin receptors that cause severe insulin resistance, and a temperature-sensitive daf-2 (a gene encoding an insulin receptor-like protein) mutant in Caenorhabditis elegans has served as an insulin resistance model. Here we report a forward chemical genetic approach with a tagged library that we used to identify a small molecule, GAPDH segregator (GAPDS), that suppresses the dauer formation induced by the daf-2 mutant. Like insulin, GAPDS increased both glucose uptake and the concentration of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) in mammalian preadipocytes. Using affinity matrices and RNA interference, we identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a GAPDS target. We discovered that GAPDH stimulates phosphatase activity against not only PtdIns(3,4,5)P(3) but also PtdIns(4,5)P(2). These results suggest that GAPDH is both an active regulator in the phosphoinositide-mediated signaling pathway and a potential new target for insulin resistance treatment.

A chemical-probe array composed of 47 off-the-shelf dyes was prepared in solution format (New York Tongue 1: NYT-1) and was tested in the identification and quantitation of 47 cation analytes, including 44 metal ions, in addition to H(+), NH(4) (+), and tetrabutylammonium (TBA). The cation solutions were tested in a series of concentrations and the fold-change in effective absorbance was analyzed by principal-component analysis (PCA), hierarchical-cluster analysis (HCA), and nearest-neighbor decision to determine both identity and quantity of the analytes. Apart from alkali-metal ions (Na(+), K(+), Li(+), Cs(+), and Rb(+)), which behave very similarly to each other due mainly to their low response, most of the cations were clearly distinguishable at 10 mM concentration. The practical detection limit of each analyte was also determined by a sequential dilution and the nearest-neighbor decision method. In the finalized working analyte concentration range (approximately 10 mM down to 0.33 microM), by considering alkali metals as one analyte group, most of the analytes were correctly identified (99.4 %). Furthermore, the success rate at which the concentration of each analyte was correctly determined was also high (96.8 %).

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We show that alpha-synuclein could assist the molecular activity of a ketoprofen-(R/S) nonspecific esterase from Archaeglobus Fulgidus. Specifically, several synthetic peptides from alpha-synuclein, each having random coil conformation in far-UV spectra, could protect the enzyme activity against stress conditions such as heat and organic solvents.