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

Abstract

AimsVariations of blood glucose level have been reported to be more harmful than sustained high glucose, but the effects on pancreatic β-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. MethodsINS-1 cells were exposed to control, SHG (sustained high glucose) or IHG (intermittent high glucose) alternating every 12h for 5days. ResultsINS-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. ConculsionsIHG 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.