Glucagon-like peptide-1 (GLP-1) and exendin-4 (Ex-4) are small peptides with potent insulin secretory effect which makes them attractive drug candidates for the treatment of Type 2 diabetes mellitus (T2DM). However, the synthesis of these small peptides is difficult due to recombinant protein degradation and instability.
Human serum transferrin (hTf) is an iron-transport protein that has great potential as an efficient carrier system for protein-based drugs. The use of hTf as a fusion partner will provide a new strategy to enhance the therapeutic potential of GLP-1 and Ex-4. This project investigates the development of transgenic tobacco plants as bioreactors for generating recombinant fusion proteins, GLP-1 - hTf and Ex-4 - hTf. Here, transgenic tobacco plants have successfully accumulated recombinant fusion proteins. Plant-derived proteins showed stability in simulated gastrointestinal environment and confirmed their ability to stimulate insulin secretion from a pancreatic (l-cell line in vitro. Lastly, hTf-fused proteins were shown to internalize into human intestinal epithelial cells in vitro. Collectively, the results suggest that transgenic plants are an effective expression and delivery system of recombinant anti-diabetic proteins
