Increase of INS-1 cell apoptosis under glucose fluctuation and the involvement of FOXO-SIRT pathway.

ABSTRACT

AIMS: Variations of blood glucose level have been reported to be more harmful than sustained high glucose, but the effects on pancreatic ß-cells have not yet been clarified. FOXO transcription factors are important for cell fate. We tried to clarify the effect of glucose variability on INS-1 cells, and the potential mechanisms related with FOXO-SIRT pathway. METHODS: INS-1 cells were exposed to control, SHG (sustained high glucose) or IHG (intermittent high glucose) alternating every 12 h for 5 days. RESULTS: INS-1 cells in SHG showed lower apoptosis and higher GSIS than IHG. Deacetylated FOXO and binding with SIRT were higher in SHG than IHG. Administration of PI3K inhibitor and/or SIRT inhibitor increased apoptosis and decreased Mn-SOD and Bcl-2 in SHG. CONCLUSIONS: [corrected] IHG was more harmful to INS-1 cells than SHG. The degree of phosphorylation and acetylation of FOXO transcription factors were different between SHG and IHG, which might be one mechanism of increased INS-1 cell apoptosis in IHG.