| 王良宸,龚燕平,李春霖,祖 源,万丽娟,孙般若,李 剑.中心粒周蛋白对胰岛素分泌的调节作用及其机制[J].现代生物医学进展英文版,2017,17(18):3406-3412. |
| 中心粒周蛋白对胰岛素分泌的调节作用及其机制 |
| The Mechanism of the Pericentrin in Regulating Insulin Secretion |
| Received:December 11, 2016 Revised:January 13, 2017 |
| DOI：10.13241/j.cnki.pmb.2017.18.002 |
| 中文关键词: 中心粒周蛋白 胰岛β细胞 胰岛素 双相分泌 |
| 英文关键词: Pericentrin Pancreaticβ-cell Insulin Biphasic secretion |
| 基金项目:国家自然科学基金面上项目（81373458） |
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| 中文摘要: |
| 摘要 目的：探讨中心粒周蛋白（pericentrin，PCNT）对胰岛素双相分泌的调节作用及其机制。方法：构建在小鼠胰岛β细胞中PCNT表达减少的转基因鼠（△PCNTβ小鼠），检测△PCNTβ小鼠与正常对照小鼠在给予糖耐量试验后第一时相和第二时相血糖和胰岛素分泌情况。检测两组小鼠胰岛内PCNT、胰岛素、纤维肌动蛋白（F-actin）变化情况，以及相关蛋白表达情况。结果：Western blot和RT-PCR显示△PCNTβ小鼠胰尾组织PCNT表达较对照组明显减低，免疫荧光提示△PCNTβ小鼠胰岛内PCNT、胰岛素表达较对照组明显减低。行腹腔注射葡萄糖耐量试验（Intraperitoneal glucose tolerance tests，IPGTT）△PCNT?茁小鼠第一时相血糖曲线下面积（Quantification of area under the curve，AUC）显著高于对照组，第二时相血糖AUC两组小鼠间无统计学差异。△PCNTβ小鼠空腹胰岛素水平与对照组比较明显升高，葡萄糖刺激胰岛素分泌（Glucose stimulated insulin secretion，GSIS）后15 min胰岛素增加值显著低于对照组，30 min和120 min时胰岛素水平与对照组无显著差异。Western blot显示△PCNTβ小鼠与对照组比较F-actin表达明显减低，ERK、p-ERK表达明显升高。RT-PCR测定△PCNTβ小鼠与对照组比较ETV4表达显著升高。免疫荧光提示△PCNTβ小鼠胰岛内F-actin和突触融合蛋白4（Syntaxin4，Syn-4）表达较对照组明显减低。结论：抑制小鼠胰岛β细胞内PCNT表达后，其通过抑制F-actin和Syn-4表达影响胰岛素分泌，导致空腹时胰岛素过度分泌和第一时相胰岛素分泌受损。 |
| 英文摘要: |
| ABSTRACT Objective: To study the effect of pericentrin(PCNT) on biphasic insulin secretion and its mechanism. Methods: Transgenic mice(△PCNTβ mice) were established with the reduction expression of PCNT in pancreatic β-cells. The blood glucose and insulin levels of the △PCNTβ and control mice were detected after glucose tolerance tests. PCNT, insulin, F-actin and other related factors were detected. Results: Western blotting and RT-PCR suggested that the expression of PCNT was significantly lower in △PCNTβ mice than in control group. Immunofluorescence suggested that the expressions of PCNT and insulin were significantly lower in △PCNTβ mice than in control group. Intraperitoneal glucose tolerance test(IPGTT) showed that the first-phase of glucose quantification of area under the curve(AUC) was significantly higher in △PCNTβ mice than in control group, however no statistical difference of the second-phase of glucose AUC was observed between the two group. The fasting insulin level was significantly higher in △PCNTβ mice than in control group, but the change of insulin level at 15 min in GSIS was significantly lower in △PCNTβ mice than in control group. There was no statistical difference of the insulin levels were observed at 30 min and 120 min in IGPTT between the two group. Western blotting suggested that the level of F-actin was significantly lower in △PCNTβ mice than in control group, while the level of ERK and p-ERK were significantly higher in △PCNTβ mice than in control group. RT-PCR suggested that the expression of ETV4 was significantly higher in △PCNTβ mice than in control group. Immunofluorescence suggested that the expression of F-actin and Syn-4 were significantly lower in △PCNTβ mice than in control group. Conclusion: Inhibition of PCNT expression in pancreatic beta cells could lead to low expression of F-actin and Syn-4, resulting in excessive insulin secretion in the fasting phase and impaired insulin secretion in the first phase. |
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