Five new alpha-pyrones, cryptowratones A-E (1-5), and five known congeners (6-10), together with four other known compounds 11-14 were isolated from the twigs of Cryptocarya wrayi. The structures of the new compounds were elucidated on the basis of extensive spectroscopic data analysis and ECD calculations. All alpha-pyrones except 6 were evaluated for their stimulatory effects on glucose uptake in vitro with CHO-K1/GLUT4 cells. The positive control insulin displayed an approximate 42 +/- 0.14% promotion on glucose uptake at 25 mu M, compared with the CHO-K1/GLUT4 group. Compounds 1a/2a, 2, 3, and 10 showed a more significant stimulation of glucose uptake than insulin (25 mu M) by 36 +/- 0.08%, 27 +/- 0.12%, 28 +/- 0.12%, and 25 +/- 0.12% at 1.5 mu M, respectively. Immunofluorescence assays indicated the glucose uptake-stimulatory activity of alpha-pyrones might be correlated with increased GLUT4 translocation.