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

被引：6

作者：

Zhang, Hanlin ^{[1
,2
]}

Dong, Meng ^{[1
]}

Yuan, Shouli ^{[1
]}

Jin, Wanzhu ^{[1
]}

机构：

[1] Chinese Acad Sci, Inst Zool, Key Lab Anim Ecol & Conservat Biol, 1 West Beichen Rd 5, Beijing 100101, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

来源：

BIOTECHNOLOGY LETTERS | 2022年 / 44卷 / 10期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

A8SGLP-1; db; GLP-1; Lactococcus lactis; Type; 2; diabetes; GLP-1 RECEPTOR AGONISTS; LACTOCOCCUS-LACTIS; GENE-EXPRESSION; PROTEIN; SECRETION; INSULIN; EXENATIDE; DELIVERY; HORMONE;

D O I：

10.1007/s10529-022-03288-1

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：1149 / 1162

页数：14

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