The neurosurvival factor Humanin inhibits beta-cell apoptosis via signal transducer and activator of transcription 3 activation and delays and ameliorates diabetes in nonobese diabetic mice.
The neurosurvival factor Humanin inhibits beta-cell apoptosis via signal transducer and activator of transcription 3 activation and delays and ameliorates diabetes in nonobese diabetic mice.
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DOI：
10.1016/j.metabol.2009.08.001
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Lee KW
中科院分区：
文献类型：
--
作者：
Hoang PT;Park P;Cobb LJ;Paharkova-Vatchkova V;Hakimi M;Cohen P;Lee KW
胰腺细胞凋亡在1型糖尿病的发病机制和潜在治疗中起重要作用。在NOD模型中，我们研究了Humanin（一种最近被描述的神经元存活因子）是否可以改善β细胞的存活并延缓或治疗糖尿病。人血素可降低血清饥饿诱导的NIT-1细胞凋亡和细胞因子处理诱导的细胞凋亡。Humanin在24小时内诱导Stat3和ERK磷酸化。Stat3的特异性抑制使Humanin的保护作用失效。糖尿病NOD小鼠治疗6周后，胰淋巴细胞浸润减少，严重程度降低。此外，Humanin延缓/预防NOD小鼠治疗20周后的糖尿病发作。综上所述，Humanin治疗在体外减少了细胞因子诱导的β细胞凋亡，并在体内改善了NOD小鼠的葡萄糖耐量和糖尿病发病。这表明Humanin可能在糖尿病相关治疗的频谱中对胰岛保护和生存有用。
Pancreatic beta cell apoptosis is important in the pathogenesis and potential treatment of Type 1 diabetes. We investigated whether Humanin, a recently described survival factor for neurons, could improve the survival of beta cells and delay or treat diabetes in the NOD model. Humanin reduced apoptosis induced by serum starvation in NIT-1 cells and decreased apoptosis induced by cytokine treatment. Humanin induced Stat3 and ERK phosphorylation over a 24 hour time course. Specific inhibition of Stat3 resulted in nullifying the protective effect of Humanin. Humanin normalized glucose tolerance in diabetic NOD mice treated for 6-weeks and their pancreata revealed decreased lymphocyte infiltration and severity. In addition, Humanin delayed/prevented the onset of diabetes in NOD mice treated for 20 weeks. In summary, Humanin treatment decreases cytokine-induced apoptosis in beta cells in vitro and improved glucose tolerance and onset of diabetes in NOD mice in vivo. This indicates that Humanin may be useful for islet protection and survival in a spectrum of diabetes-related therapeutics.
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DOI：
10.1073/pnas.0710931105
发表时间：
2008-01-15
影响因子：
11.1
作者：
Mziaut, Hassan;Kersting, Stephan;Solimena, Michele
通讯作者：
Solimena, Michele
影响因子：
7.7
作者：
García-Ocaña, A;Vasavada, RC;Stewart, AF
通讯作者：
Stewart, AF
影响因子：
7.7
作者：
HAMAGUCHI, K;GASKINS, HR;LEITER, EH
通讯作者：
LEITER, EH
影响因子：
64.8
作者：
Guo, B;Zhai, DY;Reed, JC
通讯作者：
Reed, JC
影响因子：
6.1
作者：
Hashimoto, Y;Suzuki, H;Matsuoka, M
通讯作者：
Matsuoka, M