GDF11 Attenuates Development of Type 2 Diabetes via Improvement of Islet β-Cell Function and Survival
GDF11 Attenuates Development of Type 2 Diabetes via Improvement of Islet β-Cell Function and Survival
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GDF11 通过改善胰岛 β 细胞功能和存活来减缓 2 型糖尿病的发展
DOI：
10.2337/db17-0086
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发表时间：
2017-07-01
期刊：
影响因子：
7.7
通讯作者：
Xiang, Guangda
中科院分区：
文献类型：
--
作者：
Li, Huan;Li, Yixiang;Xiang, Guangda
生长分化因子11 （GDF11）参与了胰岛发育和各种衰老状况的调节，但对成人胰岛中GDF11的生理功能知之甚少。本研究表明，在非遗传性和遗传性2型糖尿病（T2D）小鼠模型中，系统补充GDF11不仅可以保持胰岛素分泌，还可以改善β细胞的存活和形态，并改善葡萄糖代谢。相反，抗gdf11单克隆抗体治疗可引起β细胞衰竭和致死性T2D。用重组GDF11体外处理小鼠离体胰岛和MIN6细胞可减轻糖毒性诱导的β细胞功能障碍和凋亡。从机制上讲，gdf11介导的保护作用可归因于转化生长因子- β /Smad2和磷脂酰肌醇-4,5-二磷酸3-激酶- akt - fox01信号的激活。这些发现表明，GDF11的补充可能会改善β细胞的功能和质量，从而可能导致一种新的治疗方法。
Growth differentiation factor 11 (GDF11) has been implicated in the regulation of islet development and a variety of aging conditions, but little is known about the physiological functions of GDF11 in adult pancreatic islets. Here, we showed that systematic replenishment of GDF11 not only preserved insulin secretion but also improved the survival and morphology of beta-cells and improved glucose metabolism in both nongenetic and genetic mouse models of type 2 diabetes (T2D). Conversely, anti-GDF11 monoclonal antibody treatment caused beta-cell failure and lethal T2D. In vitro treatment of isolated murine islets and MIN6 cells with recombinant GDF11 attenuated glucotoxicity-induced beta-cell dysfunction and apoptosis. Mechanistically, the GDF11-mediated protective effects could be attributed to the activation of transforming growth factor-beta/Smad2 and phosphatidylinositol-4,5-bisphosphate 3-kinase-AKT-FoxO1 signaling. These findings suggest that GDF11 repletion may improve beta-cell function and mass and thus may lead to a new therapeutic approach for T2D.