Islets:科學家發現特殊基因可重新激活產胰島素β細胞表達

2015年6月11日 訊 /生物谷BIOON/ --近日，刊登在國際雜誌Islets上的一篇研究論文中，來自博裡漢姆揚大學的研究人員通過研究發現，一種特殊基因或可幫助闡明糖尿病發病的根源；目前在全球範圍內高血糖影響著4億人的健康，為了深入研究這種特殊基因的功能，研究人員轉向了對患糖尿病的學生進行研究。

文章中研究者對4名患有1型糖尿病的學生進行研究，學生患病和飲食及生活方式均無關聯，研究者Tessem說道，這項研究中我們調查了可以激活胰島β細胞的分子途徑，β細胞是可以產生胰島素的胰腺細胞，然而在1型糖尿病中這些細胞往往會被機體免疫系統所攻擊並破壞。文章中所發現的特殊基因不僅可以促進β細胞複製，而且可以幫助其維持識別葡萄糖及分泌胰島素的能力。

研究者的目的是想鑑別出所有可以促進β細胞複製的基因，這或許就可以幫助研究人員設計新型藥物來激活或關閉這些特殊基因的表達；如果給予糖尿病患者β細胞或許就可以幫助治療患者的疾病；當前將β細胞植入到糖尿病患者體內的方法包括將產生β細胞的小島植入到患者機體中，而為了使得植入的胰島產生足夠的β細胞，一位患者或許需要兩個小島結構。

因此理解誘導β細胞生長的途徑或許可以幫助降低患者對胰島的需求，從而就為開發新型療法來促進β細胞的複製生長提供一定的幫助；當然研究者同時還指出，我們並不必擔心胰島素的注射或者血糖升高，本文研究對於理解個體患糖尿病的發病機制，以及後期開發特殊療法來預防及治療糖尿病將帶來巨大幫助。（生物谷Bioon.com）

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Aurora Kinase A is critical for the Nkx6.1 mediated β-cell proliferation pathway

Amanda Hobsona, Carrie Draneya, Andrew Stratforda, Thomas C Beckerb, Danhong Lub, Michelle Arlottob & Jeffery S Tessema*

Type 1 and type 2 diabetes are ultimately characterized by depleted β-cell mass. Characterization of the molecular pathways that control β-cell proliferation could be harnessed to restore these cells. The homeobox β-cell transcription factor Nkx6.1 induces β-cell proliferation by activating the orphan nuclear receptors Nr4a1 and Nr4a3. Here, we demonstrate that Nkx6.1 localizes to the promoter of the mitotic kinase AURKA (Aurora Kinase A) and induces its expression. Adenovirus mediated overexpression of AURKA is sufficient to induce proliferation in primary rat islets while maintaining glucose stimulated insulin secretion. Furthermore, AURKA is necessary for Nkx6.1 mediated β-cell proliferation as demonstrated by shRNA mediated knock down and pharmacological inhibition of AURKA kinase activity. AURKA preferentially induces DNA replication in β-cells as measured by BrdU incorporation, and enhances the rate of histone H3 phosphorylation in primary β-cells, demonstrating that AURKA induces the replicative and mitotic cell cycle phases in rat β-cells. Finally, overexpression of AURKA results in phosphorylation of the cell cycle regulator p53, which targets p53 for degradation and permits cell cycle progression. These studies define a pathway by which AURKA upregulation by Nkx6.1 results in phosphorylation and degradation of p53, thus removing a key inhibitory factor and permitting engagement of the β-cell proliferation pathway.