Construction of a dietary-cure Saccharomyces cerevisiae expressing long-acting glucagon-like peptide-1 and investigation of its hypoglycemic activity in type 2 diabetes mellitus mouse model

ABSTRACT

Bio-drug is a new type of beneficial biology expressing therapeutic peptides (protein) as orally administrated medicine totreat diseases, in particular, chronic diseases like diabetes. In order to develop recombinant yeast strains as a bio-drug whichcould effectively ameliorate type 2 diabetes, an integrating expression vector pNK1-PGK that could successfully expressgreen fluorescent protein (GFP) in Saccharomyces cerevisiae was constructed to demonstrate the normality of the function.A pNK1-PGK vector, which expresses 10 tandem repeats of long-acting glucagon-like peptide-1(10laGLP-1), was clonedand then transformed into the S. cerevisiae INVSc1. The long-acting GLP-1 hypoglycemic yeast (LHY168) that grewrapidly and expressed 10laGLP-1 stably was screened by uracil-deficient plates and Western blot. The expression quantityof 10laGLP-1 reached 1.56 mg/g cell wet weight. Moreover, the oral administration of LHY168 significantly declined theblood glucose in type 2 diabetic mice that were constructed through co-induction of streptozotocin (STZ) and high-fat andhigh-sugar diet.