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http://purl.uniprot.org/citations/27656410http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27656410http://www.w3.org/2000/01/rdf-schema#comment"

Objective

The enteroendocrine hormone glucagon-like peptide 1 (GLP-1) is an attractive anti-diabetic therapy. Here, we generated a recombinant Lactococcus lactis strain genetically modified to produce GLP-1 and investigated its ability to improve glucose tolerance in mice on chow or high-fat diet (HFD).

Methods

We transformed L. lactis FI5876 with either empty vector (pUK200) or murine GLP-1 expression vector to generate LL-UK200 and LL-GLP1, respectively, and determined their potential to induce insulin secretion by incubating primary islets from wild-type (WT) and GLP-1 receptor knockout (GLP1R-KO) mice with culture supernatant of these strains. In addition, we administered these strains to mice on chow or HFD. At the end of the study period, we measured plasma GLP-1 levels, performed intraperitoneal glucose tolerance and insulin tolerance tests, and determined hepatic expression of the gluconeogenic genes G6pc and Pepck.

Results

Insulin release from primary islets of WT but not GLP1R-KO mice was higher following incubation with culture supernatant from LL-GLP1 compared with LL-UK200. In mice on chow, supplementation with LL-GLP1 versus LL-UK200 promoted increased vena porta levels of GLP-1 in both WT and GLP1R-KO mice; however, LL-GLP1 promoted improved glucose tolerance in WT but not in GLP1R-KO mice, indicating a requirement for the GLP-1 receptor. In mice on HFD and thus with impaired glucose tolerance, supplementation with LL-GLP1 versus LL-UK200 promoted a pronounced improvement in glucose tolerance together with increased insulin levels. Supplementation with LL-GLP1 versus LL-UK200 did not affect insulin tolerance but resulted in reduced expression of G6pc in both chow and HFD-fed mice.

Conclusions

The L. lactis strain genetically modified to produce GLP-1 is capable of stimulating insulin secretion from islets and improving glucose tolerance in mice."xsd:string
http://purl.uniprot.org/citations/27656410http://purl.org/dc/terms/identifier"doi:10.1016/j.molmet.2016.06.006"xsd:string
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/author"Lee Y.S."xsd:string
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/author"Wegmann U."xsd:string
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/author"Narbad A."xsd:string
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/author"Drucker D.J."xsd:string
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/author"Backhed F."xsd:string
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/author"Arora T."xsd:string
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/author"Greiner T.U."xsd:string
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/author"Bobhate A."xsd:string
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/name"Mol Metab"xsd:string
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/pages"725-730"xsd:string
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/title"Microbially produced glucagon-like peptide 1 improves glucose tolerance in mice."xsd:string
http://purl.uniprot.org/citations/27656410http://purl.uniprot.org/core/volume"5"xsd:string
http://purl.uniprot.org/citations/27656410http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27656410
http://purl.uniprot.org/citations/27656410http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/27656410
http://purl.uniprot.org/uniprot/#_B7ZP48-mappedCitation-27656410http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27656410
http://purl.uniprot.org/uniprot/#_Q104P0-mappedCitation-27656410http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27656410
http://purl.uniprot.org/uniprot/#_Q3ZAW0-mappedCitation-27656410http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27656410
http://purl.uniprot.org/uniprot/#_O35659-mappedCitation-27656410http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/27656410
http://purl.uniprot.org/uniprot/O35659http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/27656410
http://purl.uniprot.org/uniprot/Q104P0http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/27656410
http://purl.uniprot.org/uniprot/Q3ZAW0http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/27656410
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