University of Groningen
Metabolic and mitogenic functions of fibroblast growth factor 1 Struik, Dicky
DOI:
10.33612/diss.133879075
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Publication date: 2020
Link to publication in University of Groningen/UMCG research database
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Struik, D. (2020). Metabolic and mitogenic functions of fibroblast growth factor 1. University of Groningen. https://doi.org/10.33612/diss.133879075
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fibroblast growth factor 1
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The research described in this thesis was carried out at the Laboratory of Pediatrics (Head: prof. dr. F. Kuipers), Section Molecular Metabolism and Nutrition, University Medical Center Groningen, The Netherlands. The research was funded by grants from the Dutch Diabetes Foundation (grant 2012.00.1537 to J.W.J.), The Netherlands Organization for Scientific Research (VIDI grant 016.126.338 to J.W.J. and VICI grant 016.176.640 to J.W.J.), the De Cock Stichting, and European Foundation for the Study of Diabetes (award supported by EFSD/Novo Nordisk). The printing of this thesis was financially supported by the University of Groningen, the University Medical Center Groningen, and the Groningen University Institute for Drug Exploration.
Cover design: by Dicky Struik created with BioRender.com (front: human FGF1 at 1.10Å) ISBN (print): 978-94-034-2879-6
ISBN (online): 978-94-034-2880-2
Printing: Ridderprint BV, www.ridderprint.nl
Copyright © Dicky Struik. All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means without the permission of the author and the copyright holders of the published articles.
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Metabolic and mitogenic functions
of fibroblast growth factor 1
Proefschrift
ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen
op gezag van de
rector magnificus prof. dr. C. Wijmenga en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op
woensdag 14 oktober om 12:45 uur
door
Dirk Struik
geboren op 15 mei 19844
Promotores
Prof. dr. J.W. Jonker Prof. dr. H.J. VerkadeCopromotor
dr. J.K. KruitBeoordelingscommissie
Prof. dr. A.J.A. van de Sluis Prof. dr. M.A.T.M. van Vugt Prof. dr. E. Kalkhoven5 Roos E. Eilers
Qui, sul bordo di quel che sappiamo, a contatto con l'oceano di quanto non sappiamo, brillano il mistero del mondo, la bellezza del mondo, e ci lasciano senza fiato – Carlo Rovelli, Sette Brevi Lezioni di Fisica (Here, on the edge of what we know, in contact with the ocean of the unknown, shines the mystery and beauty of the world. And it’s breathtaking – Carlo Rovelli,
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Contents
Chapter 1: Introduction ... 7
Chapter 2: Fibroblast Growth Factors in control of lipid metabolism: from biological function to clinical application ... 39
Chapter 3: Pegbelfermin (BMS-986036): an investigational PEGylated Fibroblast Growth Factor 21 Analogue for the treatment of Non-Alcoholic Steatohepatitis (NASH) ... 57
Chapter 4: Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of non-alcoholic fatty liver disease ... 75
Chapter 5: Discovery-based proteomics identifies ApoB as a target of recombinant fibroblast growth factor 1 ... 99
Chapter 6: Fibroblast growth factor 1 normalizes glucose metabolism in ob/ob mice by enhancing beta-adrenergic activity ... 117
Chapter 7: FGF1 stimulates acute and chronic glucose uptake via MEK1/2-dependent regulation of GLUT1 and GLUT4 in 3T3-L1 adipocytes ... 139
Chapter 8: A single mutation in the heparin-binding site of fibroblast growth factor 1 leads to uncoupling of DNA synthesis and mitosis ... 157
Chapter 9: Validation of peptide-based tyrosine kinase and phosphatase activity micro-arrays to study fibroblast growth factor 1 signaling ... 175
Chapter 10: Profiling of the fibroblast growth factor system in post-mortem hypothalamus tissue of lean and obese humans ... 193
Chapter 11: Discussion ... 211 Summary ... 235 Samenvatting ... 239 Dankwoord ... 245 Curriculum vitae ... 251 Publications ... 253
