Oral glucagon-like peptide 1 analogue ameliorates glucose intolerance in db/db mice

  • Biotechnol Lett. 2022 Oct;44(10):1149-1162. doi: 10.1007/s10529-022-03288-1.
Hanlin Zhang  #  1  2 ,  Meng Dong  #  1 ,  Shouli Yuan  #  1 ,  Wanzhu Jin  3
Affiliations
  • 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. [email protected].
  • # Contributed equally.
PMID: 36006576 DOI: 10.1007/s10529-022-03288-1
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.

Keywords
A8SGLP-1; GLP-1; Lactococcus lactis; Type 2 diabetes; db/db.
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