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Description

The samples were acquired at 25 C according to literature procedure using a Biacore X100 instrument equipped with a CM5 sensor chip (GE Healthcare Biosciences) 48

GLP-1 7-36 is a 30 amino acid peptide derived from the proglucagon molecule that is synthesised in intestinal L cells, as well as in alpha cells of the pancreas and in neuronal clusters of the central nervous system (CNS).2 It is a peptide with a short half-life (23 min), due to rapid renal clearance and degradation by the enzyme dipeptidyl peptidase-4 (DPP-4), which converts GLP-1 into GLP-1 9-36, a form that does not interact with the GLP-1 receptor.1 The GLP-1 receptor (GLP-1R) belongs to the class B G protein-coupled glucagon receptor family.2,3 Activation of the Gs subunit leads to stimulation of adenylate cyclase, synthesis of cyclic AMP, mobilisation of intracellular calcium, and glucose-dependent insulin release by pancreatic beta cells.2,3 Intracellular signalling also involves various additional pathways, such as recruitment of beta-arrestin-1, which modulates receptor internalisation and desensitisation, as well as the effects of certain GLP-1R agonists.3,4 Depending on the structure of the ligand, intracellular signalling pathways are modulated towards cyclic AMP generation, activation of kinase cascades (ERK), and beta-arrestin-1 recruitment, all of which influence the biological effect and desensitisation of the GLP-1 receptor.4 Some GLP-1R agonists exhibit biased agonism, favouring intracellular activation of cyclic AMP with reduced beta-arrestin recruitment, which results in less GLP-1R desensitisation and a more prolonged biological action (Table 1)