A. Tomas

Molecular mapping and functional validation of GLP-1R cholesterol binding sites in pancreatic beta cells

This study identifies and validates cholesterol binding sites on GLP-1R in pancreatic beta cells, showing their role in receptor function and potential for drug design.

GLP-1R associates with VAPB and SPHKAP at ERMCSs to regulate β-cell mitochondrial remodelling and function

This study shows GLP-1R agonists improve mitochondrial health in beta-cells by forming a complex with VAPB and SPHKAP at ER-mitochondria MCSs, leading to mitochondrial remodelling and improved function.

Control of human pancreatic beta cell kinome by GLP-1R biased agonism

This study compares kinase activity profiles in human pancreatic beta cells stimulated by GLP-1R agonists with different bias, revealing distinct kinomic responses and potential therapeutic targets.

OSBP-mediated PI(4)P-cholesterol exchange at endoplasmic reticulum-secretory granule contact sites controls insulin secretion

The paper shows OSBP-mediated lipid exchange at ER-secretory granule contacts regulates insulin secretion by controlling cholesterol levels and is influenced by PI(4)P, VAPs, and Sac2.

An examination of the divergent spatiotemporal signaling of GLP-1R versus GIPR in pancreatic beta cells

This study compares the trafficking and signaling of GLP-1R and GIPR in pancreatic beta cells, revealing differences in internalization, recycling, and subcellular activity.

Divergent acute versus prolonged pharmacological GLP-1R responses in adult beta cell-selective β-arrestin 2 knockout mice

This study examines GLP-1R responses in beta cell-specific β-arrestin 2 knockout mice, finding acute deficits and prolonged effects with certain agonists.

Expression of mini-G proteins specifically halt cognate GPCR trafficking and intracellular signalling

This paper shows that mini-G proteins block GPCR trafficking and signaling by preventing receptor internalization, and proposes a nanobody-based alternative assay.

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.

Testosterone enhances GLP-1 efficacy at the plasma membrane and endosomes to augment insulin secretion in male pancreatic β cells

This paper shows testosterone enhances GLP-1's ability to increase insulin secretion in male β cells by boosting cAMP production at the plasma membrane and endosomes.

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 type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis

This study identifies STARD10 as a phosphoinositide binding protein that regulates insulin granule biogenesis in beta-cells by affecting phosphatidylinositol levels and proinsulin processing.

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.

LUXendins reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics

The paper introduces LUXendin peptides that label and visualize endogenous GLP1R with high specificity, revealing receptor organization and dynamics.

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.