RESEARCH ARTICLE
A Proficient Approach to the Production of Therapeutic Glucagon-Like Peptide-1 (GLP-1) in Transgenic Plants
M. Brandsma1, X. Wang1, H. Diao2, 3, S.E. Kohalmi1, A.M. Jevnikar2, 3, S. Ma1, 2, 3, *
Article Information
Identifiers and Pagination:
Year: 2009Volume: 3
First Page: 57
Last Page: 66
Publisher ID: TOBIOTJ-3-57
DOI: 10.2174/1874070700903010057
Article History:
Received Date: 26/01/2009Revision Received Date: 06/05/2009
Acceptance Date: 21/05/2009
Electronic publication date: 16/7/2009
Collection year: 2009
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Glucagon-like peptide-1 (GLP-1) is a small peptide hormone with potent insulinotropic activity and represents a promising new therapeutic tool for the treatment of diabetes. Like many other therapeutic peptides, GLP-1 is commonly produced using chemical synthesis methods, but is limited by product quantity and cost. The advent of recombinant DNA technology offers the possibility of producing GLP-1 inexpensively and in vast quantities. In this study, transgenic plants were used as a recombinant expression platform for the production of GLP-1 as a large multimeric protein. A synthetic gene encoding ten sequential tandem repeats of GLP-1 sequence (GLP-1x10) was produced and introduced into tobacco plants. Transcriptional expression of the GLP1x10 gene in transgenic plants was confirmed by RT-PCR. Western blot analysis showed that the GLP-1x10 protein efficiently accumulated in transgenic plants, with an accumulation level as high as 0.15% of total soluble protein in leaves. Importantly, insulin secretion assays using a mouse pancreatic β cell line (MIN6), showed that plant-derived GLP-1 in its synthetic decamer form, retained its ability to stimulate cellular insulin secretion, although with reduced efficacy. These results demonstrate that transgenic plants are an efficient system for the production of a multimerized recombinant GLP-1. Moreover, transgenic plants synthesizing high levels of GLP-1x10 may prove to be an attractive delivery system for direct oral administration of a novel stable GLP-1 analog in the treatment of patients with Type 2 diabetes.
