The role of the transcription factor ETV5 in insulin exocytosis.
The role of the transcription factor ETV5 in insulin exocytosis.
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DOI：
10.1007/s00125-013-3096-5
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发表时间：
2014-02
期刊：
影响因子：
8.2
通讯作者：
Seeley, Randy J.
中科院分区：
文献类型：
--
作者：
Gutierrez-Aguilar, Ruth;Kim, Dong-Hoon;Casimir, Marina;Dai, Xiao-Qing;Pfluger, Paul T.;Park, Jongsun;Haller, April;Donelan, Elizabeth;Park, Jisoo;D'Alessio, David;Woods, Stephen C.;MacDonald, Patrick E.;Seeley, Randy J.
关键词：
全基因组关联研究揭示了转录因子 ETS 变异基因 5 (ETV5) 与人类肥胖的关联。然而，它在葡萄糖稳态和能量平衡中的作用尚不清楚。每周监测 Etv5 敲除 (KO) 小鼠的体重 (BW) 和食物摄入量。在 8 周和 16 周龄时测量身体成分。研究了葡萄糖代谢，并在体内和体外测量了葡萄糖刺激的胰岛素分泌。与采用食物饮食的野生型对照小鼠相比，Etv5 KO 小鼠体形更小、更瘦，体重和脂肪量也更低。当暴露于高脂肪饮食时，KO 小鼠对饮食引起的体重增加具有抵抗力。尽管胰岛素敏感性较高，但 KO 小鼠的糖耐量严重受损，与胰岛素分泌受损有关。形态测量分析显示，Etv5 KO 小鼠的胰岛中胰岛较小，β 细胞大小也减小。在胰岛素分泌细胞系或来自人类供体的β细胞中敲低ETV5显示出完整的线粒体和Ca2+通道活性，但胰岛素胞吐作用降低。这项工作揭示了 ETV5 在体外和体内特异性调节胰岛素分泌中的关键作用。
Genome-wide association studies have revealed an association of the transcription factor ETS variant gene 5 (ETV5) with human obesity. However, its role in glucose homeostasis and energy balance is unknown. Etv5 knockout (KO) mice were monitored weekly for body weight (BW) and food intake. Body composition was measured at 8 and 16 weeks of age. Glucose metabolism was studied, and glucose-stimulated insulin secretion was measured in vivo and in vitro. Etv5 KO mice are smaller and leaner, and have a reduced BW and lower fat mass than their wild-type controls on a chow diet. When exposed to a high-fat diet, KO mice are resistant to diet-induced BW gain. Despite a greater insulin sensitivity, KO mice have profoundly impaired glucose tolerance associated with impaired insulin secretion. Morphometric analysis revealed smaller islets and a reduced beta cell size in the pancreatic islets of Etv5 KO mice. Knockdown of ETV5 in an insulin-secreting cell line or beta cells from human donors revealed intact mitochondrial and Ca2+ channel activity, but reduced insulin exocytosis. This work reveals a critical role for ETV5 in specifically regulating insulin secretion both in vitro and in vivo.
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影响因子：
--
作者：
GIORDANO, E;CIRULLI, V;MEDA, P
通讯作者：
MEDA, P
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
2.6
作者：
Kobberup, Sune;Schmerr, Martin;Dang, My-Linh;Nyeng, Pia;Jensen, Jan N.;MacDonald, Raymond J.;Jensen, Jan
通讯作者：
Jensen, Jan
影响因子：
4.6
作者：
Brent, AE;Tabin, CJ
通讯作者：
Tabin, CJ
基因组和生化洞察ETS转录因子的特异性。
影响因子：
16.6
作者：
Hollenhorst PC;McIntosh LP;Graves BJ
通讯作者：
Graves BJ