酿酒酵母孢子作为GLP-1载体的研究

Yeast Spore as Carrier for Glucagon-Like Peptide-1

DOI：10.3969/j.issn.1673-1689.2019.12.006

中文关键词: 糖尿病 胰高血糖素样肽-1 酿酒酵母 孢子 胰岛素

英文关键词: diabetes,GLP-1,yeast,spore,insulin

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中文摘要:

胰高血糖素样肽-1(Glucagon-like peptide-1，GLP-1)的口服给药研究已成为目前抗糖尿病研究领域的热点之一。本文通过对GLP-1进行基因改造和优化，并以酿酒酵母孢子作为保护和运输载体，将GLP-1表达到酿酒酵母孢子内，使GLP-1能在口服给药过程中抵抗胃肠道消化酶的降解以提高其生理活性。结果表明，GLP-1被成功表达到酿酒酵母孢子内，表达GLP-1的孢子经模拟肠胃液处理后与胰岛β细胞MIN6细胞共培养可显著提高MIN6细胞胰岛素分泌量。本研究利用酿酒酵母孢子作为载体，提高了GLP-1的抗酶解能力和促胰岛素活性，为进一步开发治疗糖尿病口服药物奠定了基础。

英文摘要:

Oral administration of GLP-1（Glucagon-like peptide-1）has attracted attention as treatment for diabetes. GLP-1 is a short peptide and secreted by L cells.GLP-1 can increase insulin release and reduce blood sugar .However，one of the major limitation of native GLP-1 is its rapid degradation by DPP-4，leading to its short half-life in vivo. In this study，we examine whether yeast spores were used as a carrier of GLP-1. Sporulation will happen when yeast cell face nutrient limitation，and previous work has shown that the yeast spores can hold secretory proteins in the periplasmic space of the spore wall because its outer layers work as a diffusion barrier. By being held in the spore wall，the proteins are protected from environmental stresses. Yeast spores were used as carrier to protect GLP-1 from being digested by gastric and intestine juice.The results showed that GLP-1 was successfully expressed in yeast spores. After pre-treated with simulated gastric and intestine juice，spores with GLP-1 obviously enhanced insulin secretion from MIN6 cells compared with GLP-1. Using yeast spores as carrier，the anti-protease degradation ability and insulinotropic activity of GLP-1 were significantly enhanced. Our study will lay a foundation for further development of oral anti-diabetic drugs.

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