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University of Groningen Role of hepatic glucose signaling in the development of liver disease Lei, Yu

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University of Groningen

Role of hepatic glucose signaling in the development of liver disease

Lei, Yu

DOI:

10.33612/diss.126530476

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date: 2020

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Lei, Y. (2020). Role of hepatic glucose signaling in the development of liver disease. University of Groningen. https://doi.org/10.33612/diss.126530476

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Role of Hepatic Glucose Signaling in the

Development of Liver Disease

(3)

The work in this thesis was carried out at the Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands and the Department of Pathology, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Shantou University Medical College, Shantou, China.

Printing of this thesis was financially supported by: University of Gronigen

University Medical Center Groningen (UMCG)

Groningen University Institute for Drug Exploration (GUIDE)

Cover design: Yu Lei Layout: Yu Lei

Printed by: Ridderprint | www.ridderprint.nl ISBN: 978-94-6375-923-6

© Yu Lei, 2020.

All rights reserved. No part of this thesis may be reproduced, distributed, stored in a retrieval system, of transmitted in any form or by any means without prior permission of the author.

Role of hepatic glucose signaling in

the development of liver disease

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans. This thesis will be defended in public on Wednesday 10 June 2020 at 9.00 hours

by

Yu Lei

born on 24 February 1989 in Chongqing, China

(4)

The work in this thesis was carried out at the Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands and the Department of Pathology, Provincial Key Laboratory of Infectious Diseases and Immunopathology, Collaborative and Creative Center, Shantou University Medical College, Shantou, China.

Printing of this thesis was financially supported by: University of Gronigen

University Medical Center Groningen (UMCG)

Groningen University Institute for Drug Exploration (GUIDE)

Cover design: Yu Lei Layout: Yu Lei

Printed by: Ridderprint | www.ridderprint.nl ISBN: 978-94-6375-923-6

© Yu Lei, 2020.

All rights reserved. No part of this thesis may be reproduced, distributed, stored in a retrieval system, of transmitted in any form or by any means without prior permission of the author.

Role of hepatic glucose signaling in

the development of liver disease

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans. This thesis will be defended in public on Wednesday 10 June 2020 at 9.00 hours

by

Yu Lei

born on 24 February 1989 in Chongqing, China

(5)

Promotores

Prof. dr. F. Kuipers Prof. dr. J. Gu

Co-Promotor

Dr. M.H. Oosterveer

Assessment Committee

Prof. dr. C.J. de Vries Prof. dr. P. Olinga Prof. dr. A.J. Moshage

Content

Chapter 1 General Introduction 7

Chapter 2 Hepatic ChREBP activation limits NAFLD development in a

mouse model for Glycogen Storage Disease type Ia 29

Chapter 3 Glucose-6-phosphate regulates hepatic bile acid synthesis

in mice 61

Chapter 4 ChREBP promotes hepatocyte proliferation in vitro but protects against oncogenic hepatocyte transformation in a mouse model for Glycogen Storage Disease type 1a

93

Chapter 5 Glucose-6-phosphatase deficiency shifts the balance between hepatocyte hyperplasia and hypertrophy during liver regeneration

125

Chapter 6 Expressions of Carbohydrate Response Element Binding Protein and Glucose Transporters in Liver Cancer and Clinical Significance

143

Chapter 7 General Discussion 161

Appendices English summary

Nederlandse samenvatting Acknowledgements Biography List of publications 181 185 189 193 195

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Promotores

Prof. dr. F. Kuipers Prof. dr. J. Gu

Co-Promotor

Dr. M.H. Oosterveer

Assessment Committee

Prof. dr. C.J. de Vries Prof. dr. P. Olinga Prof. dr. A.J. Moshage

Content

Chapter 1 General Introduction 7

Chapter 2 Hepatic ChREBP activation limits NAFLD development in a

mouse model for Glycogen Storage Disease type Ia 29

Chapter 3 Glucose-6-phosphate regulates hepatic bile acid synthesis

in mice 61

Chapter 4 ChREBP promotes hepatocyte proliferation in vitro but protects against oncogenic hepatocyte transformation in a mouse model for Glycogen Storage Disease type 1a

93

Chapter 5 Glucose-6-phosphatase deficiency shifts the balance between hepatocyte hyperplasia and hypertrophy during liver regeneration

125

Chapter 6 Expressions of Carbohydrate Response Element Binding Protein and Glucose Transporters in Liver Cancer and Clinical Significance

143

Chapter 7 General Discussion 161

Appendices English summary

Nederlandse samenvatting Acknowledgements Biography List of publications 181 185 189 193 195

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7

Chapter

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