Display of quintuple glucagon‐like peptide 1 (28–36) nonapeptide on Bacillus subtilis spore for oral administration in the treatment of type 2 diabetes

Aims To develop an oral delivery system of glucagon-like peptide 1 (GLP-1) (28-36) for treating type-2 diabetes, B.S-GLP-1(28-36), a recombinant Bacillus subtilis spores transformed with a plasmid vector encoding five consecutive GLP-1 (28-36) nonapeptides with an enterokinase site was constructed. Methods and results GLP-1(28-36) nonapeptide was successfully expressed on the surface of B. subtilis spores and validated by Western blot and immunofluorescence. The therapeutic effect of oral administration of B.S-GLP-1(28-36) spores was evaluated in type 2 diabetic model mice. The efficacy of recombinant spores was examined for a period of 13 weeks after oral administration in diabetic mice. At the end of the sixth week, diabetic mice with oral administration of BS-GLP-1(28-36) spores showed decreased blood glucose levels from 2·4 × 10- 2 mol l-1 to 1·7 × 10- 2 mol l-1 . By the ninth week, the mean fasting blood glucose level in the experimental group was significantly lower than that in the control group 30 min after injection of pyruvate. At the end of the 10th week of oral administration, the blood glucose of the experimental group was significantly lower than that of the control group after intraperitoneal injection of glucose. By the 12th week, fasting blood glucose level and fasting insulin level were measured in all mice, the results showed that the recombinant spores increased the insulin sensitivity of mice. Conclusions The results of pathological observation showed that the recombinant spores also had a certain protective effect on the liver and islets of mice, and the content of GLP-1(28-36) in the pancreas of the experimental group was increased. Significance and impact of the study The results of this study revealed that GLP-1(28-36) nonapeptides can reduce blood glucose and play an important role in the treatment of type 2 diabetes.