Yeast Spore as Carrier for Glucagon-Like Peptide-1

Abstract:

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.