Amyloid b oligomer-induced @entity1366 -dependent serine 636/639 phosphorylation of @entity10175 impairs insulin signaling and glycogen storage in XXXX astrocytes.

@entity1 @entity10175 @entity4286 @entity1366 @entity9459
AIMS: This study is to investigate the effect of amyloid b1-42 oligomers on insulin signaling in astrocytes. METHODS: Synthetic Ab1-42 oligomers were prepared and the oligomeric form of Ab1-42 was verified by an electron microscope. Normal @entity1 astrocytes were cultured in Dulbecco's Modified Eagle Medium. Western blotting was employed to measure the amount of lysate proteins. Immunofluorescence was performed to detect the distribution of phosphorylated @entity10175 and expression of P- @entity9459 in astrocytes under confocal microscopy and fluorescent microscopy, respectively. Periodic Acid-Schiff staining was used to detect glycogen, the content of which was measured using glycogen assay. RESULTS: Our data showed that Ab1-42 oligomers inhibited insulin-induced serine phosphorylation of Akt at 473 and @entity9459 at serine 9, as well as glycogen storage. However, the levels of phosphorylated @entity9459 at tyrosine 216 were significantly increased in the presence of Ab1-42 oligomers. In addition, the levels of phosphorylated @entity1366 and @entity10175 at serine 636/639 were significantly increased in response to treatment with Ab1-42 oligomers. Of note, the responses and inhibitory effects of Ab1-42 oligomers on insulin signaling were partially reversed by @entity1366 upstream inhibitor @entity4286 . CONCLUSIONS: Our results demonstrated that Ab1-42 oligomers impaired insulin signaling and suppressed insulin-induced glycogen storage in @entity1 astrocytes, probably due to @entity1366 -dependent serine phosphorylation of @entity10175 at 636/639 induced by Ab1-42 oligomers.
