Influence of amylin on apoptosis of human pancreatic islet β-cells and its molecular mechanism |
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Authors: | WANG Da-wang QUAN Jin-xing SHEN Fei-xia ZHENG Jing-chen NI Lian-song WU Jian-bo |
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Institution: | 1.Department of Endocrinology,2Medical Research Institute, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China |
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Abstract: | AIM: To investigate the molecular mechanism of amylin in inducing apoptosis of human pancreatic islet β-cells. METHODS: Human pancreatic islet cells were isolated and cultured. The cells were treated with amylin or amylin and aminoguanidine (AG group) for 24 h, respectively. Apoptosis of pancreatic islet β-cells was studied by in situ TUNEL method combined with double staining for insulin and ELISA. The levels of insulin, NO2-/NO3- and glutathione (GSH), p53 mRNA and bcl-2 mRNA were also detected. RESULTS: (1) The enrichment factor and the apoptosis rate of pancreatic islet β-cells in amylin group were markedly higher than that in control group and AG group (P<001). (2) The insulin level in amylin group was significantly lower than that in control group and AG group (P<005). (3) The levels of NO2-/NO3- and p53 mRNA in amylin group were significantly higher than that in control group and AG group (P<001), while the levels of GSH and bcl-2 mRNA were markedly decreased as compared with control group and AG group. CONCLUSIONS: Amylin increases apoptosis of human pancreatic islets β cells, resulting in decrease in insulin secretion. This may be due to increased expression of p53 and decreased expression of bcl-2 during the of oxidative stress induced by amylin. |
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