Objective To investigate the effects of tubacin, a specific inhibitor of HDAC6,on insulin secretion of β cell, and to explore the possible mechanism. Methods The expression profile of HDACs in MIN6 was observe by RT-FCR and the expression of HDAC6 in MIN6 cell and mice islet was observed by immunocytochemiatry simueltaneously. After MIN6 cells in 24-cells plates were incubated with tubacin for 24h in the presence of 5. 6 and 25 mmol/L glucose, the culture medium was taken for insulin assay with RIA. MTT was used to observe the effect of tubacin on MIN6 cell viability. The expression of insulin gene in MIN6 cultured in the same condition as described above was observe by RT-PCR immunoeytochemiatry and Western blot technique were used to observe the effect of tubacin on the level of acetylation of α-tubulin. Results The expression levels of different member of HDACs were significantly different in MIN6, and HDAC6 was expressed relatively high. Furthermore, HDAC6 was mainly located in cytoplasm of MIN6 cell and in β cell of mice islet IRA showed tubacin inhibited basal and glucose-stimulated insulin secretion. There was no effect of tubacin on MIN6 cell viability showed by MTT. The increment of insulin genes expression in MIN6 cell treated with tubacin and 25mmol/L glucose was observed by RT-PCR. Meanwhile, immunocytochemistry and Western blot technique both presented that the level of acetylation of α-tubulin in MIN6 cell was increased by treatment of tubacin , which inhibited insulin release as well. Conclusion Tubacin, the specific inhibitor of HDAC6, inhibited glucose-stimulated insulin secretion possibly by decreasing the level of acetylation of α-tubulin, which affected MIN6 cell cytoskeleton dynamics.
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