Imperial College London

DrDavidHodson

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Honorary Senior Lecturer (non-clinical)
 
 
 
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Contact

 

+44 (0)20 7594 1713d.hodson Website

 
 
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Location

 

329ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

163 results found

Peercy BE, Hodson DJ, 2024, Synchronizing beta cells in the pancreas., Elife, Vol: 13

The secretion of insulin from the pancreas relies on both gap junctions and subpopulations of beta cells with specific intrinsic properties.

Journal article

Rueckert A-K, Ast J, Hasib A, Nasteska D, Viloria K, Broichhagen J, Hodson DJet al., 2023, Fine-tuned photochromic sulfonylureas for optical control of beta cell Ca<SUP>2+</SUP> fluxes, DIABETIC MEDICINE, ISSN: 0742-3071

Journal article

Xu W, Qadir MMF, Nasteska D, Mota de Sa P, Gorvin CM, Blandino-Rosano M, Evans CR, Ho T, Potapenko E, Veluthakal R, Ashford FB, Bitsi S, Fan J, Bhondeley M, Song K, Sure VN, Sakamuri SSVP, Schiffer L, Beatty W, Wyatt R, Frigo DE, Liu X, Katakam PV, Arlt W, Buck J, Levin LR, Hu T, Kolls J, Burant CF, Tomas A, Merrins MJ, Thurmond DC, Bernal-Mizrachi E, Hodson DJ, Mauvais-Jarvis Fet al., 2023, Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells, Cell Reports, Vol: 42, Pages: 1-29, ISSN: 2211-1247

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO2, activating the HCO3--sensitive soluble adenylate cyclase; and (2) increased Gαs recruitment to GLP-1 receptor and AR complexes, activating transmembrane adenylate cyclase. Additionally, testosterone enhances GSIS in human islets via a focal adhesion kinase/SRC/phosphatidylinositol 3-kinase/mammalian target of rapamycin complex 2 actin remodeling cascade. We describe the testosterone-stimulated AR interactome, transcriptome, proteome, and metabolome that contribute to these effects. This study identifies AR genomic and non-genomic actions that enhance GLP-1-stimulated insulin exocytosis in male β cells.

Journal article

Adriaenssens A, Broichhagen J, de Bray A, Ast J, Hasib A, Jones B, Tomas A, Burgos NF, Woodward O, Lewis J, O'Flaherty E, Kimberley E, Cui C, Harada N, Inagaki N, Campbell J, Brierley D, Hodson DJ, Samms R, Gribble F, Reimann Fet al., 2023, Hypothalamic and brainstem glucose- dependent insulinotropic polypeptide receptor neurons employ distinct mechanisms to affect feeding, JCI INSIGHT, Vol: 8

Journal article

Mendive-Tapia L, Miret-Casals L, Barth ND, Wang J, de Bray A, Beltramo M, Robert V, Ampe C, Hodson DJ, Madder A, Vendrell Met al., 2023, Acid-Resistant BODIPY Amino Acids for Peptide-Based Fluorescence Imaging of GPR54 Receptors in Pancreatic Islets, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 62, ISSN: 1433-7851

Journal article

Pezhman L, Hopkin SJ, Begum J, Heising S, Nasteska D, Wahid M, Rainger GE, Hodson DJ, Iqbal AJ, Chimen M, McGettrick HMet al., 2023, PEPITEM modulates leukocyte trafficking to reduce obesity-induced inflammation, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol: 212, Pages: 1-10, ISSN: 0009-9104

Journal article

Romano N, Lafont C, Campos P, Guillou A, Fiordelisio T, Hodson DJ, Mollard P, Schaeffer Met al., 2023, Median eminence blood flow influences food intake by regulating ghrelin access to the metabolic brain, JCI INSIGHT, Vol: 8

Journal article

Viloria K, Nasteska D, Ast J, Hasib A, Cuozzo F, Heising S, Briant LJB, Hewison M, Hodson DJet al., 2023, GC-Globulin/Vitamin D-Binding Protein Is Required for Pancreatic α-Cell Adaptation to Metabolic Stress, DIABETES, Vol: 72, Pages: 275-289, ISSN: 0012-1797

Journal article

Ast J, Nasteska D, Fine NHF, Nieves DJ, Koszegi Z, Lanoiselee Y, Cuozzo F, Viloria K, Bacon A, Luu NT, Newsome PN, Calebiro D, Owen DM, Broichhagen J, Hodson DJet al., 2023, Revealing the tissue-level complexity of endogenous glucagon-like peptide-1 receptor expression and signaling, NATURE COMMUNICATIONS, Vol: 14

Journal article

Trumpp M, Oliveras A, Gonschior H, Ast J, Hodson DJ, Knaus P, Lehmann M, Birol M, Broichhagen Jet al., 2022, Enzyme self-label-bound ATTO700 in single-molecule and super-resolution microscopy, CHEMICAL COMMUNICATIONS, Vol: 58, Pages: 13724-13727, ISSN: 1359-7345

Journal article

Kravets V, Dwulet JM, Schleicher WE, Hodson DJ, Davis AM, Pyle L, Piscopio RA, Sticco-Ivins M, Benninger RKPet al., 2022, Functional architecture of pancreatic islets identifies a population of first responder cells that drive the first-phase calcium response, PLOS BIOLOGY, Vol: 20, ISSN: 1544-9173

Journal article

Birke R, Ast J, Roosen DA, Lee J, Rossmann K, Huhn C, Mathes B, Lisurek M, Bushiri D, Sun H, Jones B, Lehmann M, Levitz J, Haucke V, Hodson DJ, Broichhagen Jet al., 2022, Sulfonated red and far-red rhodamines to visualize SNAP- and Halo-tagged cell surface proteins, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 20, Pages: 5967-5980, ISSN: 1477-0520

Journal article

Cahil KN, Amin T, Boutaud O, Printz R, Newcomb DC, Foer D, Hodson DJ, Broichhagen J, Beckman JA, Yu C, Nian H, Mashayekhi M, Silver HJ, Luther JM, Brown NJ, Peebles RS, Niswender Ket al., 2022, Glucagon-Like Peptide-1 Receptor Regulates Thromboxane-Induced Activation, JACC-BASIC TO TRANSLATIONAL SCIENCE, Vol: 7, Pages: 713-715, ISSN: 2452-302X

Journal article

Michau A, Lafont C, Bargi-Souza P, Kemkem Y, Guillou A, Ravier MA, Bertrand G, Varrault A, Fiordelisio T, Hodson DJ, Mollard P, Schaeffer Met al., 2022, Metabolic Stress Impairs Pericyte Response to Optogenetic Stimulation in Pancreatic Islets, FRONTIERS IN ENDOCRINOLOGY, Vol: 13, ISSN: 1664-2392

Journal article

Mugabo Y, Zhao C, Tan JJ, Ghosh A, Campbell SA, Fadzeyeva E, Pare F, Pan SS, Galipeau M, Ast J, Broichhagen J, Hodson DJ, Mulvihill EE, Petropoulos S, Lim GEet al., 2022, 14-3-3σ Constrains insulin secretion by regulating mitochondrial function in pancreatic β cells, JCI INSIGHT, Vol: 7

Journal article

Allen SL, Seabright AP, Quinlan J, Dhaliwal A, Williams FR, Fine NHF, Hodson DJ, Armstrong MJ, Elsharkaway AM, Greig CA, Lai Y-C, Lord JM, Lavery GG, Breen Let al., 2022, The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth, CELLS, Vol: 11

Journal article

Karsai M, Zuellig RA, Lehmann R, Cuozzo F, Nasteska D, Luca E, Hantel C, Hodson DJ, Spinas GA, Rutter GA, Gerber PAet al., 2022, Lack of ZnT8 protects pancreatic islets from hypoxia- and cytokine-induced cell death, JOURNAL OF ENDOCRINOLOGY, Vol: 253, Pages: 1-11, ISSN: 0022-0795

Journal article

Guerineau NC, Campos P, Le Tissier PR, Hodson DJ, Mollard Pet al., 2022, Cell Networks in Endocrine/Neuroendocrine Gland Function, COMPREHENSIVE PHYSIOLOGY, Vol: 12, Pages: 3371-3415, ISSN: 2040-4603

Journal article

Pauza AG, Thakkar P, Tasic T, Felippe I, Bishop P, Greenwood MP, Rysevaite-Kyguoliene K, Ast J, Broichhagen J, Hodson DJ, Salgado HC, Pauza DH, Japundzic-Zigon N, Paton JFR, Murphy Det al., 2022, GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition, CIRCULATION RESEARCH, Vol: 130, Pages: 694-707, ISSN: 0009-7330

Journal article

Viloria K, Hewison M, Hodson DJ, 2022, Vitamin D binding protein/GC-globulin: a novel regulator of alpha cell function and glucagon secretion, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 600, Pages: 1119-1133, ISSN: 0022-3751

Journal article

Westbrook RL, Bridges E, Roberts J, Escribano-Gonzalez C, Eales KL, Vettore LA, Walker PD, Vera-Siguenza E, Rana H, Cuozzo F, Eskla K-L, Vellama H, Shaaban A, Nixon C, Luuk H, Lavery GG, Hodson DJ, Harris AL, Tennant DAet al., 2022, Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions, CELL REPORTS, Vol: 38, ISSN: 2211-1247

Journal article

Hoang M, Jentz E, Janssen SM, Nasteska D, Cuozzo F, Hodson DJ, Tupling AR, Fong G-H, Joseph JWet al., 2022, Isoform-specific Roles of Prolyl Hydroxylases in the Regulation of Pancreatic beta-Cell Function, ENDOCRINOLOGY, Vol: 163, ISSN: 0013-7227

Journal article

Costa A, Ai M, Nunn N, Culotta I, Hunter J, Boudjadja MB, Valencia-Torres L, Aviello G, Hodson DJ, Snider BM, Coskun T, Emmerson PJ, Luckman SM, D'Agostino Get al., 2022, Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation, MOLECULAR METABOLISM, Vol: 55, ISSN: 2212-8778

Journal article

Ast J, Broichhagen J, Hodson DJ, 2021, Reagents and models for detecting endogenous GLP1R and GIPR, EBIOMEDICINE, Vol: 74, ISSN: 2352-3964

Journal article

Olaniru OE, Cheng J, Ast J, Arvaniti A, Atanes P, Huang GC, King AJF, Jones PM, Broichhagen J, Hodson DJ, Persaud SJet al., 2021, SNAP-tag-enabled super-resolution imaging reveals constitutive and agonist-dependent trafficking of GPR56 in pancreatic -cells, MOLECULAR METABOLISM, Vol: 53, ISSN: 2212-8778

Journal article

Lucey M, Ashik T, Marzook A, Wang Y, Goulding J, Oishi A, Broichhagen J, Hodson D, Minnion J, Elani Y, Jockers R, Briddon S, Bloom S, Tomas A, Jones Bet al., 2021, Acylation of the incretin peptide exendin-4 directly impacts GLP-1 receptor signalling and trafficking, Molecular Pharmacology, Vol: 100, Pages: 319-334, ISSN: 0026-895X

The glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor and mainstay therapeutic target for the treatment of type 2 diabetes and obesity. Recent reports have highlighted how biased agonism at the GLP-1R affects sustained glucose-stimulated insulin secretion through avoidance of desensitisation and downregulation. A number of GLP-1R agonists (GLP-1RAs) feature a fatty acid moiety to prolong their pharmacokinetics via increased albumin binding, but the potential for these chemical changes to influence GLP-1R function has rarely been investigated beyond potency assessments for cyclic adenosine monophosphate (cAMP). Here we directly compare the prototypical GLP-1RA exendin-4 with its C-terminally acylated analogue, exendin-4-C16. We examine relative propensities of each ligand to recruit and activate G proteins and β-arrestins, endocytic and post-endocytic trafficking profiles, and interactions with model and cellular membranes in HEK293 and HEK293T cells. Both ligands had similar cAMP potency but exendin-4-C16 showed ~2.5-fold bias towards G protein recruitment and a ~60% reduction in β-arrestin-2 recruitment efficacy compared to exendin-4, as well as reduced GLP-1R endocytosis and preferential targeting towards recycling pathways. These effects were associated with reduced movement of the GLP-1R extracellular domain measured using a conformational biosensor approach, and a ~70% increase in insulin secretion in INS-1 832/3 cells. Interactions with plasma membrane lipids were enhanced by the acyl chain. Exendin-4-C16 showed extensive albumin binding and was highly effective for lowering of blood glucose in mice over at least 72 hours. Our study highlights the importance of a broad approach to the evaluation of GLP-1RA pharmacology.

Journal article

Cartwright DM, Oakey LA, Fletcher RS, Doig CL, Heising S, Larner DP, Nasteska D, Berry CE, Heaselgrave SR, Ludwig C, Hodson DJ, Lavery GG, Garten Aet al., 2021, Nicotinamide riboside has minimal impact on energy metabolism in mouse models of mild obesity, JOURNAL OF ENDOCRINOLOGY, Vol: 251, Pages: 111-123, ISSN: 0022-0795

Journal article

Pickford P, Lucey M, Rujan R-M, McGlone ER, Bitsi S, Ashford FB, CorrĂȘa IR, Hodson DJ, Tomas A, Deganutti G, Reynolds CA, Owen BM, Tan TM, Minnion J, Jones B, Bloom SRet al., 2021, Partial agonism improves the anti-hyperglycaemic efficacy of an oxyntomodulin-derived GLP-1R/GCGR co-agonist, Molecular Metabolism, Vol: 51, ISSN: 2212-8778

OBJECTIVE: Glucagon-like peptide-1 and glucagon receptor (GLP-1R/GCGR) co-agonism can maximise weight loss and improve glycaemic control in type 2 diabetes and obesity. In this study we investigated the cellular and metabolic effects of modulating the balance between G protein and β-arrestin-2 recruitment at GLP-1R and GCGR using oxyntomodulin (OXM)-derived co-agonists. This strategy has been previously shown to improve the duration of action of GLP-1R mono-agonists by reducing target desensitisation and downregulation. METHODS: Dipeptidyl dipeptidase-4 (DPP-4)-resistant OXM analogues were generated and assessed for a variety of cellular readouts. Molecular dynamic simulations were used to gain insights into the molecular interactions involved. In vivo studies were performed in mice to identify effects on glucose homeostasis and weight loss. RESULTS: Ligand-specific reductions in β-arrestin-2 recruitment were associated with slower GLP-1R internalisation and prolonged glucose-lowering action in vivo. The putative benefits of GCGR agonism were retained, with equivalent weight loss compared to the GLP-1R mono-agonist liraglutide in spite of a lesser degree of food intake suppression. The compounds tested showed only a minor degree of biased agonism between G protein and β-arrestin-2 recruitment at both receptors and were best classified as partial agonists for the two pathways measured. CONCLUSIONS: Diminishing β-arrestin-2 recruitment may be an effective way to increase the therapeutic efficacy of GLP-1R/GCGR co-agonists. These benefits can be achieved by partial rather than biased agonism.

Journal article

Nasteska D, Cuozzo F, Viloria K, Johnson EM, Thakker A, Bakar RB, Westbrook RL, Barlow JP, Hoang M, Joseph JW, Lavery GG, Akerman I, Cantley J, Hodson L, Tennant DA, Hodson DJet al., 2021, Prolyl-4-hydroxylase 3 maintains β cell glucose metabolism during fatty acid excess in mice, JCI INSIGHT, Vol: 6

Journal article

Marzook A, Chen S, Pickford P, Lucey M, Wang Y, CorrĂȘa Jr IR, Broichhagen J, Hodson DJ, Salem V, Rutter GA, Tan TM, Bloom SR, Tomas A, Jones Bet al., 2021, Evaluation of efficacy- versus affinity-driven agonism with biased GLP-1R ligands P5 and exendin-F1, Biochemical Pharmacology, Vol: 190, Pages: 1-12, ISSN: 0006-2952

The glucagon-like peptide-1 receptor (GLP-1R) is an important regulator of glucose homeostasis and has been successfully targeted for the treatment of type 2 diabetes. Recently described biased GLP-1R agonists with selective reductions in β-arrestin versus G protein coupling show improved metabolic actions in vivo. However, two prototypical G protein-favouring GLP-1R agonists, P5 and exendin-F1, are reported to show divergent effects on insulin secretion. In this study we aimed to resolve this discrepancy by performing a side-by-side characterisation of these two ligands across a variety of in vitro and in vivo assays. Exendin-F1 showed reduced acute efficacy versus P5 for several readouts, including recruitment of mini-G proteins, G protein-coupled receptor kinases (GRKs) and β-arrestin-2. Maximal responses were also lower for both GLP-1R internalisation and the presence of active GLP-1R-mini-Gs complexes in early endosomes with exendin-F1 treatment. In contrast, prolonged insulin secretion in vitro and sustained anti-hyperglycaemic efficacy in mice were both greater with exendin-F1 than with P5. We conclude that the particularly low acute efficacy of exendin-F1 and associated reductions in GLP-1R downregulation appear to be more important than preservation of endosomal signalling to allow sustained insulin secretion responses. This has implications for the ongoing development of affinity- versus efficacy-driven biased GLP-1R agonists as treatments for metabolic disease.

Journal article

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