S. R. Bloom

Intra-islet glucagon signalling regulates pulsatile insulin secretion and glucose homeostasis

This study shows that loss of intra-islet glucagon receptor signaling impairs glucose tolerance and insulin pulsatility in mice, suggesting glucagonergic agents could restore insulin pulsatility in T2D.

Hepatocyte cholesterol content modulates glucagon receptor signalling

This study shows that hepatocyte cholesterol content affects glucagon receptor signaling, with higher cholesterol reducing glucagon's ability to lower blood sugar in NAFLD.

Receptor Activity-Modifying Protein 2 (RAMP2) alters glucagon receptor trafficking in hepatocytes with functional effects on receptor signalling

This study investigates how RAMP2 affects GCGR trafficking and signaling in hepatocytes, showing it alters receptor internalization and signaling bias with limited metabolic impact.

Evaluation of efficacy- versus affinity-driven agonism with biased GLP-1R ligands P5 and exendin-F1

This study compares the efficacy and affinity of two GLP-1R agonists, P5 and exendin-F1, showing that exendin-F1's lower acute efficacy correlates with sustained insulin secretion and anti-hyperglycaemic effects.

Acylation of the incretin peptide exendin-4 directly impacts GLP-1 receptor signalling and trafficking

This study compares exendin-4 and its acylated variant exendin-4-C16, showing acylation affects GLP-1R signaling bias, trafficking, and pharmacokinetics.

Partial agonism improves the anti-hyperglycaemic efficacy of an oxyntomodulin-derived GLP-1R/GCGR co-agonist

This study shows that partial agonism of GLP-1R/GCGR co-agonists improves anti-hyperglycaemic efficacy by reducing β-arrestin-2 recruitment, leading to prolonged glucose-lowering effects and comparable weight loss to liraglutide.

The Vagus Nerve Mediates the Physiological but not Pharmacological Effects of PYY3-36 on Food Intake

This study shows that PYY3-36's physiological effects on food intake depend on the vagus nerve's Y2R, but pharmacological effects are not affected.

Signal bias at glucagon family receptors: rationale and downstream impacts

The paper investigates signal bias at glucagon family receptors, showing biased agonists affect intracellular signaling and insulin secretion differently.

The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists

The paper evaluates how peptide context affects GLP-1R signaling and trafficking, showing differences in agonist-mediated responses based on sequence homology and structural features.

Disconnect between signalling potency and in vivo efficacy of pharmacokinetically optimised biased glucagon-like peptide-1 receptor agonists

This study evaluates how C-terminal acylation affects GLP-1R signal bias and in vivo efficacy, finding that acylated ligands show improved therapeutic potential despite reduced potency.

Differences in signalling, trafficking and glucoregulatory properties of glucagon-like peptide-1 receptor agonists exendin-4 and lixisenatide

This study compares the signalling, trafficking, and glucoregulatory effects of exendin-4 and lixisenatide, finding differences in cAMP signalling potency and receptor recycling that impact glucose control.

Agonist binding affinity determines palmitoylation of the glucagon-like peptide-1 receptor and its functional interaction with plasma membrane nanodomains in pancreatic beta cells

This study shows that agonist binding affinity affects GLP-1R palmitoylation, nanodomain clustering, and signaling in pancreatic beta cells, influencing insulin secretion.