Oral GLP-1 Analogue Ameliorates Obesity-Induced Diabetes In Db/Db Mouse

Abstract Type 2 diabetes is currently experiencing an outbreak worldwide. GLP-1 effectively lowers blood glucose level as an emerging target for the treatment of type 2 diabetes. However, the application of GLP-1 is limited by short half-life and too expensive cost in clinic. In this study we employed the food-grade probiotics as delivery system to express human GLP-1 and its analogue. Recombinant lactococcus lactis could express GLP-1 and analogue in vitro and modified GLP-1 analogue was more resistant to DPP-4 degradation. Oral administration of GLP-1 analogue could reduce the fat mass. More importantly, GLP-1 analogue improved hyperglycemia and insulin resistance in Db/Db mouse although the insulin secretion is not observed in vitro. Our study demonstrates that lactococcus lactis genetically modified with single amino acid mutation could prolong half-life of GLP-1 and increase insulin sensitivity in Db/Db mouse model as an oral drug delivery system driving the development and innovation of drug therapy for type 2 diabetes.