Ng, Ka Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 179-204). / Abstracts in English and Chinese. / Abstract --- p.I / 摘要 --- p.IV / Publications --- p.VII / Acknowledgements --- p.VIII / Table of contents --- p.IX / List of figures --- p.XV / List of tables --- p.XVII / List of abbreviations --- p.XVIII / Chapter Chapter 1 --- General Introduction / Chapter 1.1 --- The Pancreas --- p.2 / Chapter 1.1.1 --- Anatomy of Pancreas --- p.2 / Chapter 1.1.2 --- The Exocrine Pancreas --- p.4 / Chapter 1.1.3 --- The Endocrine Pancreas --- p.5 / Chapter 1.1.3.1 --- Structure of Islets --- p.5 / Chapter 1.1.3.2 --- "Functions of α-, β-, y-, ð-, Σ-and PP-cells in Islets" --- p.7 / Chapter 1.1.4 --- Overview of Pancreas Development --- p.9 / Chapter 1.1.4.1 --- Organ Morphology --- p.10 / Chapter 1.1.4.2 --- Cyto-differentiation --- p.12 / Chapter 1.1.4.3 --- Control by Transcriptional Factors --- p.14 / Chapter 1.1.5 --- Postnatal Pancreas Development and Regeneration --- p.18 / Chapter 1.1.5.1 --- Proliferation of Pre-existing β-cells --- p.19 / Chapter 1.1.5.2 --- Neogenesis from Precursor Cells --- p.20 / Chapter 1.1.5.3 --- Transdifferentiation of other Cells --- p.20 / Chapter 1.2 --- Diabetes Mellitus --- p.22 / Chapter 1.2.1 --- Pathophysiology of Diabetes Mellitus and Current Treatments --- p.24 / Chapter 1.2.1.1 --- Type I Diabetes Mellitus --- p.24 / Chapter 1.2.1.2 --- Type II Diabetes Mellitus --- p.25 / Chapter 1.2.1.3 --- Gestational Diabetes --- p.27 / Chapter 1.2.1.4 --- Secondary Diabetes --- p.28 / Chapter 1.3 --- Stem Cell therapy --- p.29 / Chapter 1.3.1 --- Stem Cell --- p.29 / Chapter 1.3.1.1 --- Mesenchymal Stem Sell --- p.31 / Chapter 1.3.1.2 --- Embryonic Stem Cell --- p.35 / Chapter 1.3.1.3 --- Induced Pluripotent Stem Cell --- p.36 / Chapter 1.3.2 --- Islets Engineering --- p.37 / Chapter 1.3.2.1 --- Genetic Modification --- p.37 / Chapter 1.3.2.2 --- Directed Differentiation --- p.38 / Chapter 1.3.2.3 --- Microenvironment --- p.38 / Chapter 1.3.2.4 --- In vivo Regeneration --- p.39 / Chapter 1.3.2.5 --- Cell Fusions --- p.40 / Chapter 1.3.2.6 --- Combinatory Treatments --- p.40 / Chapter 1.4 --- The Vitamin A & Vitamin D System --- p.42 / Chapter 1.4.1 --- The Vitamin A --- p.42 / Chapter 1.4.2 --- Vitamin A Metabolism --- p.44 / Chapter 1.4.3 --- Roles of vitamin A in Pancreatic Development --- p.46 / Chapter 1.4.4 --- The Vitamin D --- p.48 / Chapter 1.4.5 --- Vitamin D Metabolism --- p.49 / Chapter 1.4.6 --- Metabolic Functions of Vitamin D in Islets --- p.51 / Chapter 1.4.7 --- Cod Liver Oil --- p.53 / Chapter 1.4.8 --- Interactions between Vitamin A and Vitamin D --- p.53 / Chapter 1.5 --- The Relations of Liver and Pancreas Development --- p.55 / Chapter 1.5.1 --- Endoderm Induction for Hepatic and Pancreatic Differentiation of ESCs --- p.55 / Chapter 1.5.2 --- Bipotential Precursor Population within Embryonic Endoderm --- p.56 / Chapter 1.5.3 --- Pancreatic Islets Promote Mature Liver Hepatocytes Proliferation --- p.57 / Chapter 1.5.4 --- Transdifferentiation --- p.57 / Chapter 1.5.5 --- Transplantation in Liver Niche Promotes Maturation of Insulin-Producing Cells --- p.60 / Chapter 1.5.6 --- Neuronal Relay from the Liver to Pancreatic --- p.61 / Chapter 1.5.7 --- Development of Islets in the Nile Tilapia --- p.62 / Chapter 1.6 --- The Insulin-like Growth Factor-I (IGF1) --- p.64 / Chapter 1.6.1 --- IGF1 System --- p.64 / Chapter 1.6.2 --- IGF 1 Regulation --- p.65 / Chapter 1.6.3 --- Roles of IGF 1 in Pancreatic Development and Regeneration --- p.68 / Chapter 1.7 --- Aims and Objectives of Study --- p.70 / Chapter Chapter 2 --- General Materials and Methods / Chapter 2.1 --- Pancreatic progenitor cells (PPCs) and liver stromal cells (LSCs) isolation and cell culture --- p.72 / Chapter 2.1.1 --- Tissue procurement --- p.72 / Chapter 2.1.2 --- PPC and LSC culture --- p.72 / Chapter 2.1.3 --- "Treatments of vitamin A, vitamin D and IGF 1" --- p.76 / Chapter 2.1.4 --- "Cell culture of Caco-2, HepG2 and DU-145" --- p.76 / Chapter 2.2 --- Induction of Islet-like Cell Clusters (ICCs) Differentiation --- p.77 / Chapter 2.2.1 --- In vitro Directed Differentiation --- p.77 / Chapter 2.2.2 --- In vitro LSC Microenvironment --- p.77 / Chapter 2.3 --- RNA Expression Detection --- p.79 / Chapter 2.3.1 --- RNA isolation --- p.79 / Chapter 2.3.2 --- Reverse Transcription --- p.79 / Chapter 2.3.3 --- Polymerase Chain Reaction (PCR) --- p.80 / Chapter 2.3.4 --- Realtime PCR --- p.81 / Chapter 2.4 --- Immunocytochemistry --- p.83 / Chapter 2.5 --- Western Blotting --- p.85 / Chapter 2.5.1 --- Protein extraction and quantification --- p.85 / Chapter 2.5.2 --- Western Blotting --- p.85 / Chapter 2.6 --- Enzyme-linked Immunosorbent Assay (ELISA) --- p.87 / Chapter 2.6.1 --- Detection of cell viability --- p.87 / Chapter 2.6.2 --- Detection of cell proliferation --- p.87 / Chapter 2.6.3 --- Measurement of Cell death --- p.88 / Chapter 2.6.4 --- Measurement of IGF 1 level in condition medium --- p.89 / Chapter 2.6.5 --- Measurement of glucose induced insulin secretion --- p.90 / Chapter 2.7 --- Regeneration model --- p.92 / Chapter 2.7.1 --- Regeneration model in neonatal-STZ rat --- p.92 / Chapter 2.7.2 --- Change in IGF1 expression in pancreas and liver --- p.92 / Chapter 2.8 --- Statistical Data Analysis --- p.93 / Chapter Chapter 3 --- Vitamin D and vitamin A receptor expression and the proliferative effects of ligand activation of these receptors on the development of pancreatic progenitor cells derived from human fetal pancreas. (Stem Cell Rev. 2011;7:53-63) / Chapter 3.1 --- Abstract --- p.95 / Chapter 3.2 --- Introduction --- p.97 / Chapter 3.3 --- Materials and Methods --- p.101 / Chapter 3.3.1 --- Fetal Tissue Procurement --- p.101 / Chapter 3.3.2 --- Culture of Pancreatic Progenitor Cells --- p.101 / Chapter 3.3.3 --- RNA Expression Analysis by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) --- p.102 / Chapter 3.3.4 --- Western Blot Analysis --- p.103 / Chapter 3.3.5 --- Immunocytochemstry --- p.105 / Chapter 3.3.6 --- PPC Proliferation Assays --- p.106 / Chapter 3.3.7 --- PPC Cell Death Assays --- p.107 / Chapter 3.3.8 --- Statistical Data Analysis --- p.108 / Chapter 3.4 --- Results --- p.110 / Chapter 3.4.1 --- "Expression and Localization of RAR, VDR and RXR, CYP26 and CYP24 in PPCs" --- p.110 / Chapter 3.4.2 --- Incubation of PPC with atRA Enhances PPC Viability due to Increased Proliferation and Anti-apoptosis --- p.111 / Chapter 3.4.3 --- Incubation of PPCs with Calcitriol Enhances Viability due to Increased Proliferation --- p.111 / Chapter 3.4.4 --- Both atRA and Calcitriol Induce Up-regulation of both the RAR and the VDR but not the RXR --- p.112 / Chapter 3.4.5 --- Combination Treatment with atRA and Calcitriol on Cell Viability and NGN3 Expression --- p.112 / Chapter 3.5 --- Discussion --- p.114 / Chapter Chapter 4 --- Human fetal liver stromal cell co-culture enhances the growth and differentiation of pancreatic progenitor cells into islet-like cell clusters (In submission to Gastroenterology) / Chapter 4.1 --- Abstract --- p.128 / Chapter 4.2 --- Introduction --- p.129 / Chapter 4.3 --- Materials and Methods --- p.133 / Chapter 4.3.1 --- Use of human and animal tissues --- p.133 / Chapter 4.3.2 --- "Cell preparation, characterizations and Differentiation" --- p.133 / Chapter 4.3.3 --- Examination of PPC growth and ICC differentiation and functions with LSC co-culture --- p.133 / Chapter 4.3.3 --- Identification of growth factors and investigation of their effects --- p.134 / Chapter 4.3.4 --- Statistical Analysis --- p.135 / Chapter 4.4 --- Results --- p.136 / Chapter 4.4.1 --- "Isolation, Culture and Characterizations of LSCs" --- p.136 / Chapter 4.4.2 --- Establishment of LSC co-culture system --- p.136 / Chapter 4.4.3 --- LSC co-culture enhances PPC-derived ICC differentiation --- p.137 / Chapter 4.4.4 --- Differential expression of mRNA for cytokines and growth factors between 1st and 2nd trimester LSCs --- p.138 / Chapter 4.4.5 --- Characterization of IGF 1 receptors in PPCs and the effects of exogenous IGF1 on PPC growth and ICC differentiation --- p.139 / Chapter 4.4.6 --- Neutralizing antibodies against IGF1R inhibit ICC differentiation --- p.140 / Chapter 4.5 --- Discussion --- p.142 / Chapter 4.6 --- Supplementary Materials and Methods --- p.147 / Chapter 4.6.1 --- Cell Preparation and culture --- p.147 / Chapter 4.6.2 --- In Vitro ICC differentiation --- p.148 / Chapter 4.6.3 --- RNA expression analysis --- p.149 / Chapter 4.6.4 --- Immunocytochemistry --- p.149 / Chapter 4.6.5 --- PPC viability and cell count assays --- p.150 / Chapter 4.6.6 --- IGF1 and insulin ELISA --- p.151 / Chapter 4.6.7 --- Western blotting analysis --- p.152 / Chapter 4.6.8 --- Neonatal streptozotocin regeneration model --- p.153 / Chapter Chapter 5 --- General Discussion and Future Studies / Chapter 5.1 --- General Discussion --- p.165 / Chapter 5.1.1 --- Proliferative effects and enhance expression of NGN3 by vitamin A and vitamin D on PPC --- p.166 / Chapter 5.1.2 --- Induction of PPC derived ICCs by LSCs --- p.169 / Chapter 5.1.3 --- Potential effects of liver stroma derived IGF1 on PPC derived ICCs differentiation --- p.172 / Chapter 5.1.4 --- Significance of islet engineering in the management of diabetes --- p.174 / Chapter 5.1.5 --- Conclusions --- p.176 / Chapter 5.2 --- Future Studies --- p.177 / Chapter Chapter 6 --- Reference / Reference --- p.180

Thesis (M.S.)--University of North Carolina at Wilmington, 2006. / Includes bibliographical references (leaves: 111-115)

Specific SNPs in intronic regions of the human TCF7L2 gene are associated with an elevated risk of T2D development and progression. Several investigations have suggested a role of TCF7L2 in pancreatic β-cells. Whether this transcription factor is indeed expressed in the pancreatic islets of rodent species, however, has been a controversial issue. Here, we found that TCF7L2 mRNA level was significantly lower in the pancreas compared to the gut or Ins-1 cell line. In addition, TCF7L2 mRNA abundance in the pancreas was decreased by insulin. Finally, both TCF7 and TCF7L1 but not LEF-1 could be detected in the mouse pancreas. mRNA abundance for these two transcription factors was also decreased by insulin, and the level of TCF7, TCF7L1, and TCF7L2 mRNAs could be down-regulated by HFD. We speculate that reduced expression of these TCF genes during hyperinsulinemia may alter the Wnt signalling pathway and therefore impair the function of β-cells.

Specific SNPs in intronic regions of the human TCF7L2 gene are associated with an elevated risk of T2D development and progression. Several investigations have suggested a role of TCF7L2 in pancreatic β-cells. Whether this transcription factor is indeed expressed in the pancreatic islets of rodent species, however, has been a controversial issue. Here, we found that TCF7L2 mRNA level was significantly lower in the pancreas compared to the gut or Ins-1 cell line. In addition, TCF7L2 mRNA abundance in the pancreas was decreased by insulin. Finally, both TCF7 and TCF7L1 but not LEF-1 could be detected in the mouse pancreas. mRNA abundance for these two transcription factors was also decreased by insulin, and the level of TCF7, TCF7L1, and TCF7L2 mRNAs could be down-regulated by HFD. We speculate that reduced expression of these TCF genes during hyperinsulinemia may alter the Wnt signalling pathway and therefore impair the function of β-cells.

Thesis (M. Phil.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 92-112). Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 144-163) Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 144-163) Also available online.

Thesis (Ph. D.)--University of Lund, 1994. / "ISRN LUMEDW / MEMM-1037-SE."

Thesis (Ph. D.)--University of Lund, 1994. / "ISRN LUMEDW / MEMM-1037-SE."

Theses (Ph. D.)--Marshall University, 2004. / Title from document title page. Includes abstract. Document formatted into pages: contains xiv, 192 p. including illustrations. Bibliography: p. 157-192.