G. A. Rutter

Effects of SGLT2 Ablation or Inhibition on Corticosterone Secretion in High-Fat-Fed Mice: Exploring a Nexus with Cytokine Levels

This study investigates the effects of SGLT2 inhibition or deletion on corticosterone secretion and cytokine levels in high-fat-fed mice, revealing links between SGLT2 activity, immune modulation, and metabolic homeostasis.

Proinflammatory Cytokines Suppress Nonsense-Mediated RNA Decay to Impair Regulated Transcript Isoform Processing in Pancreatic β-Cells

This study shows proinflammatory cytokines suppress NMD activity in β-cells by downregulating UPF3B, leading to increased alternative splicing and ECM-related gene expression, which contributes to β-cell dysfunction.

A high-throughput screening approach to discover potential colorectal cancer chemotherapeutics: Repurposing drugs to disrupt 14-3-3 protein-BAD interactions

This paper uses a BRET-based high-throughput screen to identify FDA-approved drugs that disrupt 14-3-3{zeta}BAD interactions, showing potential for colorectal cancer treatment.

Multiple genetic variants at the SLC30A8 locus affect local super-enhancer activity and influence pancreatic β cell survival and function

The paper identifies multiple genetic variants at the SLC30A8 locus that influence enhancer activity and β cell function, with some variants affecting gene expression and insulin secretion.

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.

Differential CpG methylation at Nnat in the early establishment of beta cell heterogeneity

This study identifies differential CpG methylation at the Nnat gene as a mechanism establishing beta cell heterogeneity during development and its potential role in diabetes.

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.

Molecular phenotyping of single pancreatic islet leader beta cells by Flash-Seq

The paper identifies leader beta cells in pancreatic islets using Flash-Seq and finds they have a distinct transcriptome and localization compared to follower cells.

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.

The gene signatures of human alpha cells in types 1 and 2 diabetes indicate disease-specific pathways of alpha cell dysfunction

This study identifies distinct gene expression patterns in human alpha cells from type 1 and type 2 diabetes, revealing disease-specific pathways of dysfunction.

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.

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.

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.

Bariatric surgery normalizes circulating glucocorticoid levels and lowers glucocorticoid action tissue-selectively in mice

This study shows bariatric surgery lowers glucocorticoid levels and reduces tissue-specific glucocorticoid activity in mice, improving insulin sensitivity without significant weight loss.

Roles for the long non-coding RNA Pax6os1/PAX6-AS1 in pancreatic beta cell identity and function.

This study investigates the role of Pax6os1/PAX6-AS1 in beta cell identity and function, finding that its upregulation in diabetes contributes to impaired functionality and that targeting it may improve glucose homeostasis.

Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice

This study shows that reducing TCF7L2 in adipocytes impairs glucose tolerance in male mice through decreased insulin secretion, incretins, and lipid metabolism dysregulation, with effects dependent on gender, age, and diet.

Intravital imaging of islet Ca2+ dynamics reveals enhanced β cell connectivity after bariatric surgery in mice

This study uses intravital imaging to show that bariatric surgery enhances β cell connectivity and Ca2+ dynamics in mice, leading to improved glucose tolerance and insulin secretion.

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.

Sorcin stimulates Activation Transcription Factor 6α (ATF6) transcriptional activity

This study shows that sorcin enhances ATF6 transcriptional activity, which is reduced during lipotoxic stress and contributes to beta cell failure in type 2 diabetes.

Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a new regulator of insulin secretion

The paper identifies FCHSD2 as a new regulator of insulin secretion by analyzing 3D chromatin interactions at the STARD10 locus in human islets.

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.

The mitochondrial Ca2+ uniporter MCU is required for normal glucose-stimulated insulin secretion in vitro and in vivo

This study shows that the mitochondrial Ca2+ uniporter MCU is essential for normal glucose-stimulated insulin secretion in pancreatic beta-cells, both in vitro and in vivo.

Vertical sleeve gastrectomy lowers kidney SGLT2 expression in the mouse

This study shows that vertical sleeve gastrectomy reduces kidney SGLT2 expression in mice, which may explain improved glucose tolerance after bariatric surgery.

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.