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Then the development of oral GLP-1 RAs for treating T2D, and more recently, approvals of GLP-1/GIP co-agonists for T2D (in 2022) and obesity (2023)
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Receptor trafficking involves the internalisation of the active receptor: Ligand complex towards endocytic compartments, followed by its deactivation/dephosphorylation and recycling back to the cell membrane, leading to its re-sensitisation, or trafficking to lysosomal organelles for its degradation and final signal termination ( Evidence from primary mouse islets and clonal beta cells (INS-1 832/3) shows that Exenatide causes a greater amount of GLP-1R degradation compared to endogenous GLP-1, with this effect apparently due to differences in the susceptibility of the agonists for degradation by the endopeptidase endothelin converting enzyme 1 (ECE1) ( Effect of the microbiome The gut microbiome consists of trillions of microorganisms that contribute to the host digestive system, generating metabolites of which the short-chain fatty acids (SCFAs): acetate, propionate and butyrate, are primary components, produced through the fermentation of indigestible polysaccharides ( 50 for acetate, propionate and butyrate at FFA2 are 431, 290 and 371 M respectively, and at FFA3 393, 41 and 33 M ( The gut microbiome is altered in obesity and T2D, an effect known as dysbiosis, where the ratio of the main bacterial phyla ( Firmicutes and Bacteroidetes ) becomes imbalanced, reducing diversity while the relative abundance of certain bacteria, including opportunistic pathogens, increases ( n = 34) and non-responders ( n = 18) ( Bacteroides dorei and Lachnoclostridium sp , both of which are associated with anti-inflammatory immunomodulation and improved gut barrier integrity ( Mitsuokella multacida , a bacterium previously shown to produce trimethylamine oxide, which contributes to atherosclerosis formation ( SCFAs are known to indirectly influence the incretin effect ( Ex vivo analysis of both murine and human islets has linked acetate and propionate to both increased and decreased glucose-stimulated insulin secretion (GSIS) ( ex vivo rat islets can increase GSIS ( via G i negatively impacted GLP-1R function, significantly reducing Exendin-4-stimulated potentiation of insulin secretion ( Lactobacillus in their pancreas
Co-localisation and secretion of glucagon-like peptide 1 and peptide YY from primary cultured human L cells
In Multi-Ligand Simultaneous Docking Analysis of Moringa Oleifera Phytochemicals Reveals Enhanced BCL-2 Inhibition via Synergistic Action, 2024 5th International Conference on Biomedical Engineering (IBIOMED), 23-25 Oct
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