Trk-fused gene (TFG) regulates pancreatic β cell mass and insulin secretory activity.
Trk-fused gene (TFG) regulates pancreatic β cell mass and insulin secretory activity.
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DOI：
10.1038/s41598-017-13432-x
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发表时间：
2017-10-12
影响因子：
4.6
通讯作者：
Asano T
中科院分区：
文献类型：
--
作者：
Yamamotoya T;Nakatsu Y;Kushiyama A;Matsunaga Y;Ueda K;Inoue Y;Inoue MK;Sakoda H;Fujishiro M;Ono H;Kiyonari H;Ishihara H;Asano T
据报道，Trk 融合基因 (TFG) 参与 COPII 介导的囊泡转运过程，TFG 的错义突变可导致多种神经退行性疾病，包括近端显性受累的遗传性运动和感觉神经病 (HMSN-P)。 HMSN-P 与糖尿病之间的高符合率表明 TFG 在葡萄糖稳态中具有重要作用。为了检验这种可能性，产生了 β 细胞特异性 TFG 敲除小鼠（βTFG KO）。有趣的是，βTFG KO表现出明显的葡萄糖耐受不良和胰岛素分泌减少。免疫组织化学分析显示，βTFG KO 中的 β 细胞质量比对照组更小，这可能是由于 β 细胞增殖减少所致。一致地，βTFG KO 中响应高脂肪、高蔗糖 (HFHS) 饮食的 β 细胞扩增显着受损。此外，在从 βTFG KO 分离的胰岛中，葡萄糖诱导的胰岛素分泌也明显受损。电子显微镜观察显示内质网 (ER) 扩张，提示 ER 应激，并且 βTFG KO 的 β 细胞中胰岛素晶体直径较小。微阵列基因表达分析表明 TFG 耗尽的胰岛中 NF-E2 相关因子 2 (Nrf2) 及其下游基因下调。总的来说，胰腺β细胞中的TFG在维持β细胞的质量和功能方面发挥着至关重要的作用，其功能障碍会增加发生葡萄糖不耐受的倾向。
The Trk-fused gene (TFG) is reportedly involved in the process of COPII-mediated vesicle transport and missense mutations in TFG cause several neurodegenerative diseases including hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). The high coincidence ratio between HMSN-P and diabetes mellitus suggests TFG to have an important role(s) in glucose homeostasis. To examine this possibility, β-cell specific TFG knockout mice (βTFG KO) were generated. Interestingly, βTFG KO displayed marked glucose intolerance with reduced insulin secretion. Immunohistochemical analysis revealed smaller β-cell masses in βTFG KO than in controls, likely attributable to diminished β-cell proliferation. Consistently, β-cell expansion in response to a high-fat, high-sucrose (HFHS) diet was significantly impaired in βTFG KO. Furthermore, glucose-induced insulin secretion was also markedly impaired in islets isolated from βTFG KO. Electron microscopic observation revealed endoplasmic reticulum (ER) dilatation, suggestive of ER stress, and smaller insulin crystal diameters in β-cells of βTFG KO. Microarray gene expression analysis indicated downregulation of NF-E2 related factor 2 (Nrf2) and its downstream genes in TFG depleted islets. Collectively, TFG in pancreatic β-cells plays a vital role in maintaining both the mass and function of β-cells, and its dysfunction increases the tendency to develop glucose intolerance.
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TFG促进了过渡性和有效胶原蛋白分泌的组织。
影响因子：
8.8
作者：
McCaughey J;Miller VJ;Stevenson NL;Brown AK;Budnik A;Heesom KJ;Alibhai D;Stephens DJ
通讯作者：
Stephens DJ
影响因子：
12.4
作者：
Cunha, Daniel A.;Cito, Monia;Cnop, Miriam
通讯作者：
Cnop, Miriam
影响因子：
3.5
作者：
Muller, Dany;Jones, Peter M.;Persaud, Shanta J.
通讯作者：
Persaud, Shanta J.
影响因子：
4.6
作者：
Okubo H;Kushiyama A;Sakoda H;Nakatsu Y;Iizuka M;Taki N;Fujishiro M;Fukushima T;Kamata H;Nagamachi A;Inaba T;Nishimura F;Katagiri H;Asahara T;Yoshida Y;Chonan O;Encinas J;Asano T
通讯作者：
Asano T
DOI：
10.1006/bbrc.1997.6943
发表时间：
1997-07-18
影响因子：
3.1
作者：
Itoh, K;Chiba, T;Nabeshima, Y
通讯作者：
Nabeshima, Y