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Peptide LKLKLL is a more effective component of Akkermansia muciniphila which regulate glucolipid… — Gut microbes (2026)

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Artigo científico

Fonte
PubMed
Data
2026 (data por confirmar)
Área
Diabetes
Revista
Gut microbes
Autores
Yuan Li, Dasen Ye, Caiyan Fu, Xingli Huang, Qingqing Ma, Fan Zhang
PMID
42473065
DOI
10.1080/19490976.2026.2687937
Documento na fonte
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The ability of Akkermansia muciniphila (AKK) to ameliorate metabolic dysfunction has attracted increasing attention as a potential strategy for obesity and diabetes management. Moving beyond the use of live bacteria toward the identification of defined bioactive components may facilitate translational development. In this study, we found that the metabolic supernatant of AKK promoted GLP-1 and GIP secretion in STC-1 cells. Metabolomic profiling identified 54 small molecules in the AKK supernatant, among which a bioactive hexapeptide, LKLKLL, was identified. LKLKLL reduced body weight in high-fat diet-induced obese mice, improved glucose tolerance in diabetic models, enhanced GLP-1 secretion, and reduced GIP levels. Mechanistically, our data suggest that LKLKLL may interact with GPR119 and activate the Gαs/adenylate cyclase/cAMP signaling pathway, leading to increased intracellular Ca²⁺ levels. Together, these findings identify an AKK-derived peptide with GLP-1/GIP regulatory activity and provide a foundation for further investigation of its potential role in metabolic diseases modulation.