title: Oral delivery of glucagon like peptide-1 by a recombinant Lactococcus lactis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: School of Pharmacy, Notre Dame of Maryland University, Baltimore, Maryland, 21210, USA.
authors.forename: Payal
authors.initials: P
authors.lastname: Agarwal
authors.forename: Pulkit
authors.initials: P
authors.lastname: Khatri
authors.forename: Blasé
authors.initials: B
authors.lastname: Billack
authors.forename: Woon-Kai
authors.initials: WK
authors.lastname: Low
authors.forename: Jun
authors.initials: J
authors.lastname: Shao
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D004285:Dogs; D016503:Drug Delivery Systems; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000627:therapeutic use; D007328:Insulin / Q000096:biosynthesis; D050417:Insulin-Secreting Cells / Q000187:drug effects; D013294:Lactococcus lactis / Q000235:genetics*; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D008647:Mesocricetus; D051381:Rats; D011924:Rats, Zucker
chemical_list: D001786:Blood Glucose; D007328:Insulin; D052216:Glucagon-Like Peptide 1