Nicholas H. F. Fine

University of Birmingham

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Co-Authors

David J. Hodson

University of Birmingham

Daniela Nasteska

University of Birmingham

Johannes Broichhagen

Leibniz-Forschungsinstitut für Molekulare Pharmakologie

Fiona Ashford

University of Birmingham

Julia Ast

University of Birmingham

Tom Podewin

Max Planck Institute for Medical Research

Guy A. Rutter

Imperial College London

Alejandra Tomás

Imperial College London

Ben Jones

Imperial College London

Amelia K. Linnemann

Indiana University School of Medicine

Cooperative Institutions

National Institutes of Health

270

Yale University

269

Harvard University

269

Rockefeller University

256

Brigham and Women's Hospital

249

Federation of American Societies for Experimental Biology

228

University of Birmingham

Imperial College London

Centre National de la Recherche Scientifique

Hammersmith Hospital

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Glucocorticoids Reprogram β-Cell Signaling to Preserve Insulin Secretion

Diabetes (2017)

Nicholas H. F. Fine Craig Doig Yasir Elhassan Nicholas C. Vierra Piero Marchetti

Excessive glucocorticoid exposure has been shown to be deleterious for pancreatic β-cell function and insulin release. However, glucocorticoids at physiological levels are essential for many homeostatic processes, including glycemic control. We show that corticosterone and cortisol and their less active precursors 11-dehydrocorticosterone (11-DHC) and cortisone suppress voltage-dependent Ca2+ channel function and Ca2+ fluxes in rodent as well as in human β-cells. However, insulin secretion, maximal ATP/ADP responses to glucose, and β-cell identity were all unaffected. Further examination revealed the upregulation of parallel amplifying cAMP signals and an increase in the number of membrane-docked insulin secretory granules. Effects of 11-DHC could be prevented by lipotoxicity and were associated with paracrine regulation of glucocorticoid activity because global deletion of 11β-hydroxysteroid dehydrogenase type 1 normalized Ca2+ and cAMP responses. Thus, we have identified an enzymatically amplified feedback loop whereby glucocorticoids boost cAMP to maintain insulin secretion in the face of perturbed ionic signals. Failure of this protective mechanism may contribute to diabetes in states of glucocorticoid excess, such as Cushing syndrome, which are associated with frank dyslipidemia.

10.2337/db16-1356

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Citations (60)

Issue Information

The FASEB Journal (2020)

Robert D. Goldman Stephen M. Hewitt Elizabeth A. Jonas Charles E. Kahn Richard Levin

Long non-coding RNA LINC00337 induces autophagy and chemoresistance to cisplatin

10.1002/fsb2.20603

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Citations (0)

Author Correction: Super-resolution microscopy compatible fluorescent probes reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics

Julia Ast Anastasia Arvaniti Nicholas H. F. Fine Daniela Nasteska Fiona Ashford

Dynamics

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Citations (0)

Optical control of GPR40 signalling in pancreatic β-cells

Chemical Science (2017)

James A. Frank Dmytro A. Yushchenko Nicholas H. F. Fine Margherita Duca Mevlut Citir

Fatty acids activate GPR40 and K⁺ channels to modulate β-cell function.

Signalling

Signalling pathways

10.1039/c7sc01475a

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Citations (44)

Author Correction: PDX1LOW MAFALOW β-cells contribute to islet function and insulin release

Nature Communications (2021)

Daniela Nasteska Nicholas H. F. Fine Fiona Ashford Federica Cuozzo Katrina Viloria

Mice deficient in the respiratory chain gene Cox6a2

10.1038/s41467-021-24848-5

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Citations (3)

Vitamin D-binding protein is required for the maintenance of [alpha]-cell identity and function

Endocrine Abstracts (2019)

Katrina Viloria Daniela Nasteska Dean P. Larner Nicholas H. F. Fine Fiona Ashford

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Vitamin D-binding protein

Alpha (finance)

10.1530/endoabs.65.p201

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Citations (0)

Getting with Program: An ACCESS Success Story

INTESOL Journal (2015)

Nicholas H. F. Fine

An urban middle school with a large English language learner population (n=222) grapples with the complexity of the transition from the familiar LAS Links testing administration to the new WIDA ACCESS assessment for the first time in 2015. Here one of the lead ENL teachers outlines the organizational approaches developed to streamline the process and to minimize time out of mainstream classrooms for ELLs for ACCESS testing which is administered during a portion of the academic year already burdened by state-mandated ACUITY and ISTEP testing rounds

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Source

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An expanded LUXendin color palette for GLP1R detection and visualization in vitro and in vivo

Julia Ast Alissa N. Novak Tom Podewin Nicholas H. F. Fine Ben Jones

The glucagon-like peptide-1 receptor (GLP1R) is expressed in peripheral tissues and the brain, where it exerts pleiotropic actions on metabolic and inflammatory processes. Detection and visualization of GLP1R remains challenging, partly due to a lack of validated reagents. Previously, we generated LUXendins, antagonistic red and far-red fluorescent probes for specific labeling of GLP1R in live and fixed cells/tissue. We now extend this concept to the green and near-infrared color ranges by synthesizing and testing LUXendin492, LUXendin551, LUXendin615 and LUXendin762. All four probes brightly and specifically label GLP1R in cells and pancreatic islets. Further, LUXendin551 acts as chemical beta cell reporter in preclinical rodent models, while LUXendin762 allows non-invasive imaging, highlighting differentially-accessible GLP1R populations. We thus expand the color palette of LUXendins to seven different spectra, opening up a range of experiments using widefield microscopy available in most labs through super-resolution imaging and whole animal imaging. With this, we expect that LUXendins will continue to generate novel and specific insight into GLP1R biology.

Palette (painting)

10.26434/chemrxiv-2021-7rngq

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Super-resolution microscopy compatible fluorescent probes reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics

Nature Communications (2020)

Julia Ast Anastasia Arvaniti Nicholas H. F. Fine Daniela Nasteska Fiona Ashford

Abstract The glucagon-like peptide-1 receptor (GLP1R) is a class B G protein-coupled receptor (GPCR) involved in metabolism. Presently, its visualization is limited to genetic manipulation, antibody detection or the use of probes that stimulate receptor activation. Herein, we present LUXendin645 , a far-red fluorescent GLP1R antagonistic peptide label. LUXendin645 produces intense and specific membrane labeling throughout live and fixed tissue. GLP1R signaling can additionally be evoked when the receptor is allosterically modulated in the presence of LUXendin645 . Using LUXendin645 and LUXendin651 , we describe islet, brain and hESC-derived β-like cell GLP1R expression patterns, reveal higher-order GLP1R organization including membrane nanodomains, and track single receptor subpopulations. We furthermore show that the LUXendin backbone can be optimized for intravital two-photon imaging by installing a red fluorophore. Thus, our super-resolution compatible labeling probes allow visualization of endogenous GLP1R, and provide insight into class B GPCR distribution and dynamics both in vitro and in vivo.

Dynamics

10.1038/s41467-020-14309-w

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Citations (116)

Expanded LUXendin Color Palette for GLP1R Detection and Visualization In Vitro and In Vivo

JACS Au (2022)

Julia Ast Alissa N. Novak Tom Podewin Nicholas H. F. Fine Ben Jones

The glucagon-like peptide-1 receptor (GLP1R) is expressed in peripheral tissues and the brain, where it exerts pleiotropic actions on metabolic and inflammatory processes. Detection and visualization of GLP1R remains challenging, partly due to a lack of validated reagents. Previously, we generated LUXendins, antagonistic red and far-red fluorescent probes for specific labeling of GLP1R in live and fixed cells/tissues. We now extend this concept to the green and near-infrared color ranges by synthesizing and testing LUXendin492, LUXendin551, LUXendin615, and LUXendin762. All four probes brightly and specifically label GLP1R in cells and pancreatic islets. Further, LUXendin551 acts as a chemical beta cell reporter in preclinical rodent models, while LUXendin762 allows noninvasive imaging, highlighting differentially accessible GLP1R populations. We thus expand the color palette of LUXendins to seven different spectra, opening up a range of experiments using wide-field microscopy available in most labs through super-resolution imaging and whole animal imaging. With this, we expect that LUXendins will continue to generate novel and specific insights into GLP1R biology.

Palette (painting)

10.1021/jacsau.2c00130

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Citations (15)