2015年1月29日 訊 /生物谷BIOON/-- 美國Cornell University近日在Diabetes上發(fā)表了一篇有關(guān)糖尿病治療的新研究，他們讓大鼠服用改造過的表達(dá)GLP-1的乳酸桿菌,，得到了意想不到的降血糖效果,。

胰高血糖素樣肽（Glucogan-Like Peptide-1, GLP-1）是一種主要由腸道上皮細(xì)胞所產(chǎn)生的激素，屬于一種腸促胰島素（incretin）,。已知的是GLP-1有諸多生理作用包括促進(jìn)胰島B細(xì)胞分泌胰島素,，抑制胰島α細(xì)胞分泌胰高血糖素等等。它特殊的生理作用因?yàn)橛兄谔悄虿〉闹委?，一直是糖尿病研究的熱點(diǎn),。

之前已有研究表明GLP-1一種無活性的形式GLP-1 (1-37) 能刺激大鼠和人體小腸上皮細(xì)胞轉(zhuǎn)變?yōu)橐葝uB細(xì)胞。于是Cornell大學(xué)的這個(gè)研究小組想試一試靠服用而攝入的GLP-1（1-37）能否重新“編碼”糖尿病大鼠的小腸上皮細(xì)胞,，使其變?yōu)橐葝uB細(xì)胞從而減輕高血糖癥狀,。他們將含有GLP-1（1-37）的載體轉(zhuǎn)入人乳酸桿菌，然后每天為糖尿病大鼠口服這種益生菌片,。結(jié)果非常明顯：大鼠服用后,，胰島素分泌量和對(duì)血糖耐受能力明顯增加；小腸上段出現(xiàn)許多胰島素分泌細(xì)胞,，數(shù)量相當(dāng)于正常大鼠胰島B細(xì)胞的25~33%,；并且這些新胰島素分泌細(xì)胞內(nèi)檢測到胰島B細(xì)胞所特有的轉(zhuǎn)錄因子MafA，PDX-1,，F(xiàn)oxA2的表達(dá)。這表示這些細(xì)胞與B細(xì)胞極其相似,。研究人員也表示,，給正常大鼠服用這種乳酸桿菌，血糖水平?jīng)]有影響,，因?yàn)檎５拇笫笫遣恍枰~外的胰島素維持血糖水平,。

這個(gè)研究結(jié)果為將來糖尿病的治療提供了一個(gè)既安全又有效的口服藥物的選擇。實(shí)際上這項(xiàng)技術(shù)已經(jīng)獲得生產(chǎn)許可,?；蛟S在不久將來糖尿病患者只需每天早上服用一片益生菌片，就能幫助控制血糖。（生物谷Bioon.com）

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DOI：10.2337 / db14-0635

Engineered Commensal Bacteria Reprogram Intestinal Cells Into Glucose-Responsive Insulin-Secreting Cells for the Treatment of Diabetes

Franklin F. Duan, Joy H. Liu, and John C. March.

Abstract
The inactive full-length form of GLP-1(1–37) stimulates conversion of both rat and human intestinal epithelial cells into insulin-secreting cells. We investigated whether oral administration of human commensal bacteria engineered to secrete GLP-1(1–37) could ameliorate hyperglycemia in a rat model of diabetes by reprogramming intestinal cells into glucose-responsive insulin-secreting cells. Diabetic rats were fed daily with human lactobacilli engineered to secrete GLP-1(1–37). Diabetic rats fed GLP-1-secreting bacteria showed significant increases in insulin levels and, additionally, were significantly more glucose tolerant than those fed the parent bacterial strain. These rats developed insulin-producing cells within the upper intestine in numbers sufficient to replace ～25–33% of the insulin capacity of nondiabetic healthy rats. Intestinal tissues in rats with reprogrammed cells expressed MafA, PDX-1, and FoxA2. HNF-6 expression was observed only in crypt epithelia expressing insulin and not in epithelia located higher on the villous axis. Staining for other cell markers in rats treated with GLP-1(1–37)-secreting bacteria suggested that normal function was not inhibited by the close physical proximity of reprogrammed cells. These results provide evidence of the potential for a safe and effective nonabsorbed oral treatment for diabetes and support the concept of engineered commensal bacterial signaling to mediate enteric cell function in vivo.