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Articles by Guy A. Rutter
Targeting ZIP12-mediated Zn 2+ signaling as a treatment for pulmonary hypertension
Reference #1 Abstract Supplementary Materials REFERENCES AND NOTES eLetters (0) Information & Authors Metrics & Citations Check Access References Figures Tables Media Share This article has 0 eLetter . Abstract ZIP12, a membrane-bound zinc importer, is up-regulated in the remodeled pulmonary arterioles of patients with pulmonary arterial hypertension (PAH). Genetic deletion of its encoding gene, Slc39a12, ameliorates the disease in rodent models.
Pancreatic α-cells are functionally heterogeneous and sex-dependently regulated by neighboring endocrine cells
Abstract Glucose and paracrine regulation of α-cells, particularly with respect to sex differences, is still poorly understood. Here, we imaged islets from GluCre:GCaMP6f mice in pancreatic slices, additionally loaded with a red Ca²⁺ indicator, to precisely interrogate Ca²⁺ dynamics in α-cells and the adjacent β- and δ-cells. During a glucose ramp (1.8-10.8 mM), α-cell Ca²⁺ oscillations were heterogeneous, antiphasic to β-cells, and inversely correlated with δ-cells.
Pancreatic α-cells integrate immune and neuronal stimuli for insulin secretion
Keywords glucagon insulin cephalic phase IL-1β parasympathetic stimulation Research topic(s) CP: metabolism CP: neuroscience Introduction Pancreatic islets are richly innervated by the parasympathetic nervous system, and their neurotransmitter acetylcholine enhances glucose-stimulated insulin secretion via muscarinic receptors.1,2,3,4,5 However, certain neuronally driven insulin secretory processes, such as the cephalic phase insulin response (CPIR), occur independently of a rise in blood...
STARD10 regulates human pancreatic β cell differentiation and triglyceride metabolism
ReportOnline now102815Open access 1Stem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology, A∗STAR, Singapore 138673, Singapore 2Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore 3Precision Medicine Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore 4Section of Cell Biology and Functional Genomics, Imperial College London,...
In vivo functional profiling and structural characterization of the human GLP1R A316T variant
Abstract 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 missense variant, A316T, protects against T2D and cardiovascular disease. Here, we generated and characterized a human GLP1R A316T mouse model.
Publisher Correction: Exploring pancreatic beta-cell subgroups and their connectivity - Nature Metabolism
Correction to: Nature Metabolism https://doi.org/10.1038/s42255-024-01097-6, published online 8 August 2024. This paper was originally published as an Article under a Creative Commons Attribution 4.0 International license, © The Author(s), whereas it should have been published as a Review Article under standard Springer Nature license (© The Author(s), under exclusive licence to Springer Nature Limited), as is now amended in the HTML and PDF versions of the article.
Exploring pancreatic beta-cell subgroups and their connectivity - Nature Metabolism
Abstract Functional pancreatic islet beta cells are essential to ensure glucose homeostasis across species from zebrafish to humans. These cells show significant heterogeneity, and emerging studies have revealed that connectivity across a hierarchical network is required for normal insulin release. Here, we discuss current thinking and areas of debate around intra-islet connectivity, cellular hierarchies and potential “controlling” beta-cell populations.
A high-throughput screening approach to discover potential colorectal cancer chemotherapeutics: Repurposing drugs to disrupt 14-3-3 protein-BAD interactions
Abstract Inducing apoptosis in different types of cancer cells is an effective therapeutic strategy. However, the success of existing chemotherapeutics can be compromised by tumor cell resistance and systemic off-target effects. Therefore, the discovery of pro-apoptotic compounds with minimal systemic side-effects is crucial. 14-3-3 proteins are molecular scaffolds that serve as important regulators of cell survival.
Paired box 6 gene delivery preserves beta cells and improves islet transplantation efficacy
The paper explained Problem Loss of pancreatic beta cells is the central feature of all forms of diabetes. Current therapies fail to halt the declining beta cell mass. Islet transplantation is a beta cell replacement therapy adopted in clinical practice. However, post-transplant islet graft loss and insufficient supply of cadaveric islets limit the success and utility of this modality of treatment. Results This work identified PAX6 as a critical regulator of beta cell function and survival.
Editorial: The pancreatic islet - a multifaceted hub of inter-cellular communication
Islets of Langerhans are spherical clusters of endocrine cells embedded in the pancreatic parenchyma. These micro-organs are essential for the regulation of blood glucose metabolism through the release of insulin and glucagon from beta and alpha cells, respectively. The structural configuration of the islets confers a high degree of homotypic and heterotypic cell-cell contact which facilitates communication between the different cells.
The relative expression of pro- and anti-apoptotic BCL2 family members does not explain the different apoptotic thresholds of ESCs and EpiSCs To address if differences in the relative expression of pro- and anti-apoptotic BCL2 family members underpin the different apoptotic response of ESCs and EpiSCs, we compared the expression of these proteins in each cell type.
Paired box 6 programs essential exocytotic genes in the regulation of glucose-stimulated insulin secretion and glucose homeostasis
Stimulating insulin secretion Paired box 6 (PAX6) is a transcription factor involved in pancreatic development; now, So et al. report that PAX6 also indirectly regulates insulin secretion in mature pancreatic beta cells. The authors show that PAX6 promoted cAMP response element–binding protein (CREB)–mediated expression of Munc18-1/2 proteins known to be involved in core processes of exocytosis.
Comment on Satin et al. “Take Me To Your Leader”: An Electrophysiological Appraisal of the Role of Hub Cells in Pancreatic Islets. Diabetes 2020;69:830-836 | Diabetes
e-Letters: Comments and Responses Satin et al. (1) present a critique of a recent model for “hub/follower” dynamics in intra-islet regulation of insulin secretion presented in two recent articles from our laboratories (2,3).
The roles of cytosolic and intramitochondrial Ca2+ and the mitochondrial Ca2+-uniporter (MCU) in the stimulation of mammalian oxidative phosphorylation
This item requires a subscription to The Journal of Biological Chemistry.
Age matters: Grading granule secretion in beta cells
Eleni Georgiadou1 and Guy A. Rutter1,2* 1Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology, and Metabolism, Department of Metabolism, Reproduction, and Digestion, Imperial College London, London, United Kingdom 2Lee Kong Chian School of Medicine, Nan Yang Technological University, Singapore ↵* For correspondence: Guy Rutter, g.rutter{at}imperial.ac.uk. Edited by Phyllis I.
From the Fields®
By Theresa Jeffreys Bright, Colusa County farmer Pecans bloom later than most orchard crops, so I have a bit of time before the active growing season begins. Tasks for now are mowing and weed management for the tree berms. As soon as the trees start to bud out, they will have an aerial application of zinc and aphid treatment. Last season, it was hoped an additional aphid spray could be avoided, but then the orchard was invaded by black aphids.
Leader β-cells coordinate Ca2+ dynamics across pancreatic islets in vivo
Abstract Pancreatic β-cells form highly connected networks within isolated islets. Whether this behaviour pertains to the situation in vivo, after innervation and during continuous perfusion with blood, is unclear. In the present study, we used the recombinant Ca2+ sensor GCaMP6 to assess glucose-regulated connectivity in living zebrafish Danio rerio, and in murine or human islets transplanted into the anterior eye chamber.
Correction: Transcription factor-7-like 2 (TCF7L2) gene acts downstream of the Lkb1/Stk11 kinase to control mTOR signaling, β cell growth, and insulin secretion.
Correction: Transcription factor-7–like 2 (TCF7L2) gene acts downstream of the Lkb1/Stk11 kinase to control mTOR signaling, β cell growth, and insulin secretion. VOLUME 293 (2018) PAGES 14178–14189 There was a typographical error in the fourth sentence of the second paragraph of the introduction.
From the Fields®
There could be a mediocre El Niño this winter. They are up to 60 percent as far as forecasting that and it has been strengthening a little bit over the last few months. So that brings some optimism to all of California. El Niño tends to bring above-average rainfall. We would love a repeat of the winter of 2016-17. The Central Valley is wrapping up their melon harvest and we just started our melon harvest, which is a little earlier than planned by about five days.
The α-cell in diabetes mellitus
Abstract Findings from the past 10 years have placed the glucagon-secreting pancreatic α-cell centre stage in the development of diabetes mellitus, a disease affecting almost one in every ten adults worldwide. Glucagon secretion is reduced in patients with type 1 diabetes mellitus, increasing the risk of insulin-induced hypoglycaemia, but is enhanced in type 2 diabetes mellitus, exacerbating the effects of diminished insulin release and action on blood levels of glucose.
Transcription factor-7-like 2 (TCF7L2) gene acts downstream of the Lkb1/Stk11 kinase to control mTOR signaling, β cell growth, and insulin secretion
Variants in the transcription factor-7–like 2 (TCF7L2/TCF4) gene, involved in Wnt signaling, are associated with type 2 diabetes. Loss of Tcf7l2 selectively from the β cell in mice has previously been shown to cause glucose intolerance and to lower β cell mass. Deletion of the tumor suppressor liver kinase B1 (LKB1/STK11) leads to β cell hyperplasia and enhanced glucose-stimulated insulin secretion, providing a convenient genetic model for increased β cell growth and function.
Transcription factor-7-like 2 (TCF7L2) gene acts downstream of the Lkb1/Stk11 kinase to control mTOR signaling, β cell growth, and insulin secretion
Variants in the transcription factor-7-like 2 (TCF7L2/TCF4) gene, involved in Wnt signalling, are associated with type 2 diabetes. Loss of Tcf7l2 selectively from the β cell in mice has previously been shown to cause glucose intolerance and to lower β cell mass. Deletion of the tumour suppressor liver kinase B1 (LKB1/STK11) leads to β cell hyperplasia and enhanced glucose-stimulated insulin secretion, providing a convenient genetic model for increased β cell growth and function.
Local and regional control of calcium dynamics in the pancreatic islet
Ca2+ is the key intracellular regulator of insulin secretion, acting in the beta cell as the ultimate trigger for exocytosis. In response to high glucose, ATP-sensitive K+ channel closure and plasma membrane depolarisation engage a sophisticated machinery to drive pulsatile cytosolic Ca2+ changes. Voltage-gated Ca2+ channels, Ca2+-activated K+ channels and Na+/Ca2+ exchange all play important roles.
Lipid-tuned Zinc Transport Activity of Human ZnT8 Protein Correlates with Risk for Type-2 Diabetes
Zinc is a critical element for insulin storage in the secretory granules of pancreatic beta cells. The islet-specific zinc transporter ZnT8 mediates granular sequestration of zinc ions. A genetic variant of human ZnT8 arising from a single nonsynonymous nucleotide change contributes to increased susceptibility to type-2 diabetes (T2D), but it remains unclear how the high risk variant (Arg-325), which is also a higher frequency (>50%) allele, is correlated with zinc transport activity.
Lipid-tuned Zinc Transport Activity of Human ZnT8 Correlates with Risk for Type-2 Diabetes
Zinc is a critical element for insulin storage in the secretory granules of pancreatic beta cells. The islet-specific zinc transporter ZnT8 mediates granular sequestration of zinc ions. A genetic variant of human ZnT8 arising from a single nonsynonymous nucleotide change contributes to increased susceptibility to type-2 diabetes (T2D), but it remains unclear how the high-risk variant (R325), which is also a higher-frequency (>50%) allele, is correlated with zinc transport activity.
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