Guy A. Rutter
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View article: Editorial: In vivo magnetic resonance imaging of metabolic disorders
Editorial: In vivo magnetic resonance imaging of metabolic disorders Open
View article: A high-throughput screening approach to discover potential colorectal cancer chemotherapeutics: repurposing drugs to identify novel disruptors of 14-3-3 proteins
A high-throughput screening approach to discover potential colorectal cancer chemotherapeutics: repurposing drugs to identify novel disruptors of 14-3-3 proteins Open
View article: <b>Additive effects of dorzagliatin and glucagon-like peptide-1 receptor agonism in a novel mouse model of </b><b><i>GCK</i></b><b>-MODY and in obese </b><b><i>db/db</i></b><b> mice</b>
<b>Additive effects of dorzagliatin and glucagon-like peptide-1 receptor agonism in a novel mouse model of </b><b><i>GCK</i></b><b>-MODY and in obese </b><b><i>db/db</i></b><b> mice</b> Open
Glucokinase (GK) catalyses the key regulatory step in glucose-stimulated insulin secretion. Correspondingly, hetero- and homozygous mutations in human GCK cause maturity-onset diabetes of the young (GCK-MODY) and permanent neonatal …
View article: <b>Additive effects of dorzagliatin and glucagon-like peptide-1 receptor agonism in a novel mouse model of </b><b><i>GCK</i></b><b>-MODY and in obese </b><b><i>db/db</i></b><b> mice</b>
<b>Additive effects of dorzagliatin and glucagon-like peptide-1 receptor agonism in a novel mouse model of </b><b><i>GCK</i></b><b>-MODY and in obese </b><b><i>db/db</i></b><b> mice</b> Open
Glucokinase (GK) catalyses the key regulatory step in glucose-stimulated insulin secretion. Correspondingly, hetero- and homozygous mutations in human GCK cause maturity-onset diabetes of the young (GCK-MODY) and permanent neonatal …
View article: I-BET151 modulates glucokinase gene expression and beta cell function in part through changes in FOXO1 expression
I-BET151 modulates glucokinase gene expression and beta cell function in part through changes in FOXO1 expression Open
View article: Pancreatic α-cells are functionally heterogeneous and sex-dependently regulated by neighboring endocrine cells
Pancreatic α-cells are functionally heterogeneous and sex-dependently regulated by neighboring endocrine cells Open
Glucose and paracrine regulation on α-cells, particularly with respect to sex differences, remains unclear. Hence, we imaged islets of GluCre:GCaMP6f fl/fl mice in pancreatic slices, additionally loaded with a red Ca²⁺ dye, to precisely in…
View article: Binding kinetics, bias, receptor internalization and effects on insulin secretion in vitro and in vivo of a novel <scp>GLP</scp> ‐ <scp>1R</scp> / <scp>GIPR</scp> dual agonist, <scp>HISHS</scp> ‐2001
Binding kinetics, bias, receptor internalization and effects on insulin secretion in vitro and in vivo of a novel <span>GLP</span> ‐ <span>1R</span> / <span>GIPR</span> dual agonist, <span>HISHS</span> ‐2001 Open
Aims The use of incretin analogues has emerged as an effective approach to achieve both enhanced insulin secretion and weight loss in Type 2 diabetes (T2D) patients. Agonists which bind and stimulate multiple receptors have shown particula…
View article: LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes
LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes Open
View article: Effects of SGLT2 ablation or inhibition on corticosterone secretion in high-fat-fed mice: exploring a nexus with cytokine levels
Effects of SGLT2 ablation or inhibition on corticosterone secretion in high-fat-fed mice: exploring a nexus with cytokine levels Open
View article: Serine palmitoyltransferase-mediated de novo sphingolipid biosynthesis is required for normal insulin production and glucose tolerance
Serine palmitoyltransferase-mediated de novo sphingolipid biosynthesis is required for normal insulin production and glucose tolerance Open
Aims/Hypothesis The importance for normal insulin secretion of ceramide synthesis is unclear. De novo ceramide synthesis requires serine palmitoyl transferase, SPT2, encoded by Sptl2 . Methods We generated β-cell-selective Sptl2 null mice …
View article: Exploration of individual beta cell function over time <i>in vivo:</i> effects of hyperglycemia and glucagon-like peptide-1 receptor (GLP1R) agonism
Exploration of individual beta cell function over time <i>in vivo:</i> effects of hyperglycemia and glucagon-like peptide-1 receptor (GLP1R) agonism Open
The coordinated function of beta cells within the pancreatic islet is required for the normal regulation of insulin secretion and is partly controlled by specialized “leader” and highly connected “hub” beta-cell subpopulations. Whether cel…
View article: ER calcium stores contribute to glucose-induced Ca<sup>2+</sup>waves and intercellular connectivity in mouse pancreatic islets
ER calcium stores contribute to glucose-induced Ca<sup>2+</sup>waves and intercellular connectivity in mouse pancreatic islets Open
Defective insulin secretion is a hallmark of diabetes mellitus. Glucose-induced Ca 2+ oscillations are critical for the stimulation of insulin secretion, though the mechanisms through which these propagate across the islet are poorly under…
View article: Binding Kinetics, Bias, Receptor Internalization and Effects on Insulin Secretion <i>in vitro</i> and <i>in vivo</i> of a Novel GLP-1R/GIPR Dual Agonist, HISHS-2001
Binding Kinetics, Bias, Receptor Internalization and Effects on Insulin Secretion <i>in vitro</i> and <i>in vivo</i> of a Novel GLP-1R/GIPR Dual Agonist, HISHS-2001 Open
The use of incretin analogues has emerged in recent years as an effective approach to achieve both enhanced insulin secretion and weight loss in type 2 diabetes (T2D) patients. Agonists which bind and stimulate multiple receptors have show…
View article: Severe neonatal hypotonia due to <scp><i>SLC30A5</i></scp> variant affecting function of <scp>ZnT5</scp> zinc transporter
Severe neonatal hypotonia due to <span><i>SLC30A5</i></span> variant affecting function of <span>ZnT5</span> zinc transporter Open
The tightly‐regulated spatial and temporal distribution of zinc ion concentrations within cellular compartments is controlled by two groups of Zn 2+ transporters: the 14‐member ZIP/SLC39 family, facilitating Zn 2+ influx into the cytoplasm…
View article: Investigating the pathogenicity of the recessive<i>HNF1A</i>p.A251T variant in monogenic diabetes using iPSC-derived beta-like cells
Investigating the pathogenicity of the recessive<i>HNF1A</i>p.A251T variant in monogenic diabetes using iPSC-derived beta-like cells Open
Monogenic diabetes, formerly called Maturity-Onset Diabetes of the Young (MODY), involves single-gene mutations, typically with dominant inheritance, and has been associated with variants in 14 genes. Among these, HNF1A mutations are the m…
View article: Roles for the long non-coding RNA Pax6os1/PAX6-AS1 in pancreatic beta cell function
Roles for the long non-coding RNA Pax6os1/PAX6-AS1 in pancreatic beta cell function Open
Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of beta cell function. Here, we show that an lncRNA-transcribed antisense to Pax6, annotated as Pax6os1/PAX6-AS1, was upregulated by high glucose concentrations in human as …
View article: Leveraging hierarchical structures for genetic block interaction studies using the hierarchical transformer
Leveraging hierarchical structures for genetic block interaction studies using the hierarchical transformer Open
Initially introduced in 1909 by William Bateson, classic epistasis (genetic variant interaction) refers to the phenomenon that one variant prevents another variant from a different locus from manifesting its effects. The potential effects …
View article: Sex-dependent additive effects of dorzagliatin and incretin on insulin secretion in a novel mouse model of<i>GCK</i>-MODY
Sex-dependent additive effects of dorzagliatin and incretin on insulin secretion in a novel mouse model of<i>GCK</i>-MODY Open
Glucokinase (GK) catalyses the key regulatory step in glucose-stimulated insulin secretion. Correspondingly, hetero– and homozygous mutations in human GCK cause maturity-onset diabetes of the young (GCK-MODY) and permanent neonatal diabete…
View article: A high-throughput screening approach to discover potential colorectal cancer chemotherapeutics: Repurposing drugs to disrupt 14-3-3 protein-BAD interactions
A high-throughput screening approach to discover potential colorectal cancer chemotherapeutics: Repurposing drugs to disrupt 14-3-3 protein-BAD interactions Open
Selectively inducing apoptosis in cancer cells is an effective therapeutic strategy, but the reality of success of existing chemotherapeutics is compromised by emergent tumor cell resistance and systemic off-target effects. Therefore, the …
View article: <i>In vivo</i> functional profiling and structural characterisation of the human <i>GLP1R</i> A316T variant
<i>In vivo</i> functional profiling and structural characterisation of the human <i>GLP1R</i> A316T variant Open
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective therapies for type 2 diabetes (T2D) and obesity, yet patient responses are variable, with GLP1R gene variation potentially linked to therapeutic outcomes. A GLP1R natural m…
View article: SUN-146 Do highly-connected beta cell hubs overlap with epigenetically-defined BetaHi cells?
SUN-146 Do highly-connected beta cell hubs overlap with epigenetically-defined BetaHi cells? Open
G. Ostinelli: None. P. Carapeto: None. Z. Kabbash: None. E. Dror: None. J. Pospsisilik: None. G.A. Rutter: None. The adult beta cell is highly specialized and long-lived, and deploys epigenetic control to maintain its stability over time. …
View article: Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence
Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence Open
View article: Liver kinase <scp>B1</scp> ( <scp>LKB1</scp> ) regulates the epigenetic landscape of mouse pancreatic beta cells
Liver kinase <span>B1</span> ( <span>LKB1</span> ) regulates the epigenetic landscape of mouse pancreatic beta cells Open
Liver kinase B1 (LKB1/STK11) is an important regulator of pancreatic β‐cell identity and function. Elimination of Lkb1 from the β‐cell results in improved glucose‐stimulated insulin secretion and is accompanied by profound changes in gene …
View article: Optogenetic β cell interrogation in vivo reveals a functional hierarchy directing the Ca <sup>2+</sup> response to glucose supported by vitamin B6
Optogenetic β cell interrogation in vivo reveals a functional hierarchy directing the Ca <sup>2+</sup> response to glucose supported by vitamin B6 Open
Coordination of cellular activity through Ca 2+ enables β cells to secrete precise quantities of insulin. To explore how the Ca 2+ response is orchestrated in space and time, we implement optogenetic systems to probe the role of individual…
View article: Liver kinase B1 (LKB1) regulates the epigenetic landscape of mouse pancreatic beta cells
Liver kinase B1 (LKB1) regulates the epigenetic landscape of mouse pancreatic beta cells Open
Liver kinase B1 (LKB1/STK11) is an important regulator of pancreatic β-cell identity and function. Elimination of Lkb1 from the β-cell results in improved glucose-stimulated insulin secretion and is accompanied by profound changes in gene …
View article: Intra-islet glucagon signalling regulates beta-cell connectivity, first-phase insulin secretion and glucose homoeostasis
Intra-islet glucagon signalling regulates beta-cell connectivity, first-phase insulin secretion and glucose homoeostasis Open
View article: Multiple genetic variants at the <i>SLC30A8</i> locus affect local super‐enhancer activity and influence pancreatic β‐cell survival and function
Multiple genetic variants at the <i>SLC30A8</i> locus affect local super‐enhancer activity and influence pancreatic β‐cell survival and function Open
Variants at the SLC30A8 locus are associated with type 2 diabetes (T2D) risk. The lead variant, rs13266634, encodes an amino acid change, Arg325Trp (R325W), at the C‐terminus of the secretory granule‐enriched zinc transporter, ZnT8. Althou…
View article: Effects of SGLT2 Ablation or Inhibition on Corticosterone Secretion in High-Fat-Fed Mice: Exploring a Nexus with Cytokine Levels
Effects of SGLT2 Ablation or Inhibition on Corticosterone Secretion in High-Fat-Fed Mice: Exploring a Nexus with Cytokine Levels Open
Despite recent therapeutic advances, achieving optimal glycaemic control remains a challenge in managing Type 2 Diabetes (T2D). Sodium-glucose co-transporter type 2 (SGLT2) inhibitors have emerged as effective treatments by promoting urina…
View article: Glucose Regulation of β-Cell KATP Channels: Is a New Model Needed?
Glucose Regulation of β-Cell KATP Channels: Is a New Model Needed? Open
The canonical model of glucose-induced increase in insulin secretion involves the metabolism of glucose via glycolysis and the citrate cycle, resulting in increased ATP synthesis by the respiratory chain and the closure of ATP-sensitive K+…
View article: LDHB contributes to the regulation of lactate levels and basal insulin secretion in human pancreatic β cells
LDHB contributes to the regulation of lactate levels and basal insulin secretion in human pancreatic β cells Open