2015年1月29日 讯 /生物谷BIOON/-- 美国Cornell University近日在Diabetes上发表了一篇有关糖尿病治疗的新研究，他们让大鼠服用改造过的表达GLP-1的乳酸杆菌，得到了意想不到的降血糖效果。
胰高血糖素样肽（Glucogan-Like Peptide-1, GLP-1）是一种主要由肠道上皮细胞所产生的激素，属于一种肠促胰岛素（incretin）。已知的是GLP-1有诸多生理作用包括促进胰岛B细胞分泌胰岛素，抑制胰岛α细胞分泌胰高血糖素等等。它特殊的生理作用因为有助于糖尿病的治疗，一直是糖尿病研究的热点。
之前已有研究表明GLP-1一种无活性的形式GLP-1 (1-37) 能刺激大鼠和人体小肠上皮细胞转变为胰岛B细胞。于是Cornell大学的这个研究小组想试一试靠服用而摄入的GLP-1（1-37）能否重新“编码”糖尿病大鼠的小肠上皮细胞，使其变为胰岛B细胞从而减轻高血糖症状。他们将含有GLP-1（1-37）的载体转入人乳酸杆菌，然后每天为糖尿病大鼠口服这种益生菌片。结果非常明显：大鼠服用后，胰岛素分泌量和对血糖耐受能力明显增加；小肠上段出现许多胰岛素分泌细胞，数量相当于正常大鼠胰岛B细胞的25~33%；并且这些新胰岛素分泌细胞内检测到胰岛B细胞所特有的转录因子MafA，PDX-1，FoxA2的表达。这表示这些细胞与B细胞极其相似。研究人员也表示，给正常大鼠服用这种乳酸杆菌，血糖水平没有影响，因为正常的大鼠是不需要额外的胰岛素维持血糖水平。
这个研究结果为将来糖尿病的治疗提供了一个既安全又有效的口服药物的选择。实际上这项技术已经获得生产许可。或许在不久将来糖尿病患者只需每天早上服用一片益生菌片，就能帮助控制血糖。（生物谷Bioon.com）
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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.
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