Adenosine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Receptors [110]) are activated endogenous ligand adenosine (potentially inosine also at A3 receptors). Crystal structures for antagonist-bound [153, 313, 221, 61], agonist-bound [375, 203, 204] and G protein-bound A2A [49] have been described. The of an A1 receptor [128] adenosine-bound receptor-Gi complex [86] resolve...

Extensive structure activity analysis has allowed us to identify specific residues in the glucagon sequence that are responsible for either receptor recognition or signal transduction. For instance, we have demonstrated that aspartic acid 9 and histidine 1 are essential for activation, and that an ionic interaction between the negative carboxylate and the protonated imidazole may contribute to ...

β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving β-cell function and glucose tolerance and regulating g...

Recently, peptides with opioid-like activity have been demonstrated in peptic digests of dietary protein. The present study was designed to determine the effect of digested and undigested gluten on postprandial insulin and glucagon levels in conscious dogs. The intragastric instillation of digested gluten (25 g) elicited a more rapid and a significantly greater rise in postprandial peripheral v...

Since 2005, glucagon-like peptide 1 (GLP-1) receptor agonists have been clinically available, which has resulted in a significant transformation diabetes care, both terms of weight management and glucose control [...]

Abstract Background Four glucagon-like peptide-1 (GLP-1) receptor agonists that are structurally similar to human GLP-1 have been shown reduce the risk of adverse cardiovascular events among per...

BACKGROUND AND PURPOSE The glucagon-like peptide 1 (GLP-1) receptor performs an important role in glycaemic control, stimulating the release of insulin. It is an attractive target for treating type 2 diabetes. Recently, several reports of adverse side effects following prolonged use of GLP-1 receptor therapies have emerged: most likely due to an incomplete understanding of signalling complexiti...

We here report a pharmacological characterization of two new somatostatin (SS) receptor subtype-2 (sst2) selective antagonists by evaluating their GH-releasing activity when administered, by different routes, in anesthetized adult rats and in freely moving 10-d-old rats. Moreover, we describe the effect of these SS antagonists on the GH response to GHRH after short-term high-dose dexamethasone ...

Side effects from targeted drugs remain a serious concern. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which are highly homologous in sequences and have similar structures and drug-binding pockets. To identify targetable differences between paralogs, we analyzed two types (type-I and type-II) of functional divergence between two paralogs in the ...