Oral Glucagon-like Peptide 1 Analogue Ameliorates Glucose Intolerance in Db/db Mice

Overview

Journal Biotechnol Lett

Specialties Biochemistry
Biotechnology

Date 2022 Aug 25

PMID 36006576

Authors

Hanlin Zhang

Meng Dong

Shouli Yuan

Wanzhu Jin

Affiliations

Soon will be listed here.

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.

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