Squamosamide Derivative FLZ Protects Pancreatic β-Cells from Glucotoxicity by Stimulating Akt-FOXO1 Pathway.

ABSTRACT: Chronic hyperglycemia increases apoptosis and reduces glucose-stimulated insulin secretion. Although protective agents have been searched extensively, none has been found so far. Here we tested FLZ, a synthetic derivative of squamosamide from a Chinese herb, as a potential candidate for antiglucotoxicity in INS-1E cells and mouse islets. Chronic culture of β-cells in 30 mM glucose caused progressive reduction of cell viability, accompanied with increased apoptosis and reduced insulin secretion. These effects on apoptosis and insulin were reversed by FLZ in a dose-dependent manner. FLZ treatment also increased forkhead box O1 protein phosphorylation and reduced its nuclear location. On the contrary, FLZ increased pancreatic and duodenal homeobox-1 expression and its nuclear localization, an

SUBMITTER: Kong X 

PROVIDER: S-EPMC4488173 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature