Hanlin Zhang1,2, Meng Dong1, Shouli Yuan1, Wanzhu Jin3. 1. Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, 1 West Beichen Rd. No. 5, Beijing, 100101, China. 2. University of Chinese Academy of Sciences, Beijing, 100049, China. 3. Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, 1 West Beichen Rd. No. 5, Beijing, 100101, China. jinw@ioz.ac.cn.
Abstract
OBJECTIVES: We constructed a recombinant oral GLP-1 analogue in Lactococcus lactis (L. lactis) and evaluated its physiological functions. RESULTS: In silico docking suggested the alanine at position 8 substituted with serine (A8SGLP-1) reduced binding of DPP4, which translated to reduced cleavage by DPP4 with minimal changes in stability. This was further confirmed by an in vitro enzymatic assay which showed that A8SGLP-1 significantly increased half-life upon DPP4 treatment. In addition, recombinant L. lactis (LL-A8SGLP-1) demonstrated reduced fat mass with no changes in body weight, significant improvement of random glycemic control and reduced systemic inflammation compared with WT GLP-1 in db/db mice. CONCLUSION: LL-A8SGLP-1 adopted in live biotherapeutic products reduce blood glucose in db/db mice without affecting its function.
OBJECTIVES: We constructed a recombinant oral GLP-1 analogue in Lactococcus lactis (L. lactis) and evaluated its physiological functions. RESULTS: In silico docking suggested the alanine at position 8 substituted with serine (A8SGLP-1) reduced binding of DPP4, which translated to reduced cleavage by DPP4 with minimal changes in stability. This was further confirmed by an in vitro enzymatic assay which showed that A8SGLP-1 significantly increased half-life upon DPP4 treatment. In addition, recombinant L. lactis (LL-A8SGLP-1) demonstrated reduced fat mass with no changes in body weight, significant improvement of random glycemic control and reduced systemic inflammation compared with WT GLP-1 in db/db mice. CONCLUSION: LL-A8SGLP-1 adopted in live biotherapeutic products reduce blood glucose in db/db mice without affecting its function.
Authors: H M Berman; J Westbrook; Z Feng; G Gilliland; T N Bhat; H Weissig; I N Shindyalov; P E Bourne Journal: Nucleic Acids Res Date: 2000-01-01 Impact factor: 16.971
Authors: Luis G Bermúdez-Humarán; Naima G Cortes-Perez; Yves Le Loir; Alexandra Gruss; Cristina Rodriguez-Padilla; Odila Saucedo-Cardenas; Philippe Langella; Roberto Montes de Oca-Luna Journal: Biotechnol Prog Date: 2003 May-Jun