Effects Of Resveratrol Induces Sirt1 Hyperexpression On Insulin Secretion And Life Span Of NIT-1 Cells

ObjectiveTo investigate the expression profile of genes in the Insulin/IGF-1 signal pathway, under the state of hyperexpression of Sirt1 which was induced by Resveratrol in theβneoplastic cell NIT-1, and it's effect on the function and life span of NIT-1 cells. The results would provide many useful experiment evidences and rationale foundation, which would help to illuminate the pathogenesy of T2DM, and make advantages to improve the prevention and treatment of T2DM.MethodsNIT-1 cells were cultured to exponential growth phase and stimulated by Resveratrol(Re)[1], the activator of Sirt1, and LY294002(LY)[2], the blocking agent of PI3-K. Samples were divided into 4 groups: group Re, group LY, group LY and Re and group DMSO as the control. The expressions of Sirt1, Foxo1 and its targets p27, Bim and FasL were detected by RT-PCR and Immunocytochemical assay. The secretion and expression of insulin were detected by radioimmunity and Immunocytochemical assay; The cell-multiplication cycle was measured by Cytometry.Result1. Resveratrol induced Sirt1 hyperexpressing in NIT-1 cell, and extend the cell-multiplication cycle; 2. Sirt1 decreased apoptosis by regulating p27 and Bim through a way of activating the transcription activity of Foxo1; 3. The hyperexpression of Sirt1 strengthen the glucose tolerance, and improved the function of insulin secretion of NIT-1 cells which were functionally defected in PI3-K/Akt pathway.ConclusionSirt1 hyperexpression which was induced by Resverarol could delay the aged proceeding of NIT-1 cells; It was unnecessary to go through the upstream of PI3-K/Akt, Sirt1 could directly effect the activity of Foxo1, so that to regulate the insulin/IGF-1 signal pathway, strengthen the glucose tolerance, improve the conduction of insulin signal and the function of insulin secretion. Therefore, Sirt1 may participate in the generation and development of T2DM.