PURPOSE: To develop a live oral delivery system of Glucagon like peptide-1 (GLP-1), for the treatment of Type-2 Diabetes. METHODS: LL-pUBGLP-1, a recombinant Lactococcus lactis (L. lactis)) transformed with a plasmid vector encoding GLP-1 cDNA was constructed and was used as a delivery system. Secretion of rGLP-1 from LL-pUBGLP-1 was characterized by ELISA. The bioactivity of the rGLP-1 was examined for its insulinotropic activity on HIT-T15 cells. Transport of rGLP-1 across MDCK cell monolayer when delivered by LL-pUBGLP-1 was studied. The therapeutic effect of LL-pUBGLP-1 after oral administration was investigated in ZDF rats. RESULTS: DNA sequencing and ELISA confirmed the successful construction of the LL-pUBGLP-1 and secretion of the active form of rGLP-1. In vitro insulinotropic studies demonstrated that LL-pUBGLP-1 could significantly (p < 0.05) stimulate HIT-T15 cells to secrete insulin as compared to the controls. When delivered by LL-pUBGLP-1, the GLP-1 transport rate across the MDCK cell monolayer was increased by eight times (p < 0.01) as compared to the free solution form. Oral administration of LL-pUBGLP-1 in ZDF rats resulted in a significant decrease (10-20%, p < 0.05) in blood glucose levels during 2-11 h post dosing and a significant increase in insulin AUC0-11h (2.5 times, p < 0.01) as compared to the free solution. CONCLUSION: The present study demonstrates that L. lactis when genetically modified with a recombinant plasmid can be used for the oral delivery of GLP-1.
PURPOSE: To develop a live oral delivery system of Glucagon like peptide-1 (GLP-1), for the treatment of Type-2 Diabetes. METHODS: LL-pUBGLP-1, a recombinant Lactococcus lactis (L. lactis)) transformed with a plasmid vector encoding GLP-1 cDNA was constructed and was used as a delivery system. Secretion of rGLP-1 from LL-pUBGLP-1 was characterized by ELISA. The bioactivity of the rGLP-1 was examined for its insulinotropic activity on HIT-T15 cells. Transport of rGLP-1 across MDCK cell monolayer when delivered by LL-pUBGLP-1 was studied. The therapeutic effect of LL-pUBGLP-1 after oral administration was investigated in ZDFrats. RESULTS: DNA sequencing and ELISA confirmed the successful construction of the LL-pUBGLP-1 and secretion of the active form of rGLP-1. In vitro insulinotropic studies demonstrated that LL-pUBGLP-1 could significantly (p < 0.05) stimulate HIT-T15 cells to secrete insulin as compared to the controls. When delivered by LL-pUBGLP-1, the GLP-1 transport rate across the MDCK cell monolayer was increased by eight times (p < 0.01) as compared to the free solution form. Oral administration of LL-pUBGLP-1 in ZDFrats resulted in a significant decrease (10-20%, p < 0.05) in blood glucose levels during 2-11 h post dosing and a significant increase in insulin AUC0-11h (2.5 times, p < 0.01) as compared to the free solution. CONCLUSION: The present study demonstrates that L. lactis when genetically modified with a recombinant plasmid can be used for the oral delivery of GLP-1.
Authors: Lorenz Scheppler; Monique Vogel; Adrian W Zuercher; Michael Zuercher; Jacques-Edouard Germond; Sylvia M Miescher; Beda M Stadler Journal: Vaccine Date: 2002-07-26 Impact factor: 3.641
Authors: Sonal Singh; Hsien-Yen Chang; Thomas M Richards; Jonathan P Weiner; Jeanne M Clark; Jodi B Segal Journal: JAMA Intern Med Date: 2013-04-08 Impact factor: 21.873
Authors: L Steidler; K Robinson; L Chamberlain; K M Schofield; E Remaut; R W Le Page; J M Wells Journal: Infect Immun Date: 1998-07 Impact factor: 3.441