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The modulatory effects of simvastatin, a HMG CoA reductase inhibitor, on insulin release from isolated porcine pancreatic islets of Langerhans. / Modulatory effects of simvastatin, a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, on insulin release from isolated porcine pancreatic islets of Langerhans

Wong, Mei Fung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 207-251). / Abstracts in English and Chinese. / ABSTRACT --- p.i / 摘要 --- p.iv / ACKNOWLEDGEMENTS --- p.vi / PUBLICATIONS BASED ON WORK IN THIS THESIS --- p.vii / ABBREVIATIONS --- p.viii / TABLE OF CONTENTS --- p.x / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Diabetes Mellitus --- p.1 / Chapter 1.2 --- Structure and Functions of the Pancreas --- p.2 / Chapter 1.2.1 --- Size of Pancreatic β-Cells --- p.4 / Chapter 1.2.2 --- Signaling Pathways of Insulin Secretion from Pancreatic β-Cells --- p.4 / Chapter 1.3 --- Classification of Diabetes --- p.6 / Chapter 1.3.1 --- Type 1 Diabetes --- p.6 / Chapter 1.3.2 --- Type 2 Diabetes --- p.8 / Chapter 1.4 --- Pathologies of Type 2 Diabetes --- p.9 / Chapter 1.4.1 --- Hyperglycemia --- p.9 / Chapter 1.4.1.1 --- A dvanced Glycosylation End Products --- p.11 / Chapter 1.4.1.2 --- Protein Kinase C Activation --- p.13 / Chapter 1.4.1.3 --- The Glucosamine Pathway --- p.14 / Chapter 1.4.1.4 --- Oxidative Stress --- p.15 / Chapter 1.4.2 --- Insulin Resistance --- p.15 / Chapter 1.4.3 --- Loss of β-Cell Mass and β-Cell Dysfunction --- p.18 / Chapter 1.5 --- Complications of Diabetes Mellitus --- p.21 / Chapter 1.5.1 --- Cardiovascular Diseases --- p.21 / Chapter 1.5.2 --- Diabetic Retinopathy --- p.22 / Chapter 1.5.3 --- Diabetic Nephropathy --- p.23 / Chapter 1.5.4 --- Neuropathy --- p.24 / Chapter 1.6 --- Anti-Diabetic Drugs for Type 2 Diabetes Mellitus --- p.25 / Chapter 1.6.1 --- Secretagogues --- p.25 / Chapter 1.6.2 --- Sensitizers --- p.26 / Chapter 1.6.3 --- Alpha-Glucosidase Inhibitors --- p.27 / Chapter 1.6.4 --- Peptide Analogs --- p.27 / Chapter 1.6.4.1 --- Incretin Mimetics --- p.27 / Chapter 1.6.4.2 --- Dipeptidyl Peptidase-4 Inhibitors --- p.28 / Chapter 1.7 --- Insights of Porcine Islets in Treatment of Diabetics --- p.28 / Chapter 1.8 3 --- -Hydroxy-3-Methylglutaryl Coenzyme A Reductase (HMG CoA Reductase) --- p.31 / Chapter 1.8.1 --- Statins --- p.32 / Chapter 1.8.2 --- Pleiotropic Effects of Statins --- p.36 / Chapter 1.8.2.1 --- Statins and Isoprenylated Proteins --- p.36 / Chapter 1.8.2.2 --- Statins and Endothelial Functions --- p.38 / Chapter 1.8.2.3 --- Statins and Platelet Functions --- p.39 / Chapter 1.8.2.4 --- Statins and Plaque Stability --- p.39 / Chapter 1.8.2.5 --- Statins and Vascular Inflammation --- p.40 / Chapter 1.9 --- Clinical Studies of Statins on Diabetics --- p.41 / Chapter 1.10 --- Possible Factors Involved in Simvastatin-Regulated Insulin Secretion --- p.44 / Chapter 1.10.1 --- AMP-Activated Protein Kinase --- p.44 / Chapter 1.10.2 --- Caveolin-1 --- p.46 / Chapter 1.10.3 --- Sterol-Regulatory Elementary Binding Protein --- p.50 / Chapter 1.10.4 --- Protein Phosphatase 2A --- p.52 / Chapter 1.10.5 --- Calcium Sensing Receptor --- p.55 / Chapter 1.11 --- Objectives of Study --- p.59 / Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.60 / Chapter 2.1 --- Materials --- p.60 / Chapter 2.1.1 --- Solutions --- p.60 / Chapter 2.1.2 --- Antibodies --- p.63 / Chapter 2.2 --- Methods --- p.64 / Chapter 2.2.1 --- Maintenance of Pancreas Function --- p.64 / Chapter 2.2.2 --- Islet Isolation --- p.65 / Chapter 2.2.3 --- Hematoxylin and Eosin (H&E) Staining --- p.65 / Chapter 2.2.4 --- Simvastatin and Simvastatin-Na+ --- p.66 / Chapter 2.2.5 --- AICAR --- p.67 / Chapter 2.2.6 --- Compound C --- p.67 / Chapter 2.2.7 --- Incubation of Islets --- p.67 / Chapter 2.2.8 --- Western Blot --- p.68 / Chapter 2.2.9 --- Enzyme-Linked Immunosorbent Assay (ELISA) --- p.69 / Chapter 2.2.10 --- Statistical Analysis --- p.71 / Chapter CHAPTER 3 --- HISTOLOGY OF PORCINE PANCREATIC ISLETS OF LANGERHANS --- p.72 / Chapter 3.1 --- Comparison of Sizes of Porcine Pancreatic Islets in Histological Sections of Pancreas --- p.72 / Chapter CHAPTER 4 --- PROTEIN EXPRESSION OF HMG COA REDUCTASE --- p.75 / Chapter 4.1 --- Effect of Incubation Time on HMG CoA Reductase Expression --- p.75 / Chapter 4.2 --- Short-Term Effect of Simvastatin on HMG CoA Reductase Expression --- p.78 / Chapter 4.3 --- Long-Term Effect of Simvastatin on HMG CoA Reductase Expression --- p.81 / Chapter 4.4 --- Effect of Osmolality on HMG CoA Reductase Expression --- p.83 / Chapter 4.5 --- Effect of Simvastatin on Ser871 p-HMG CoA Reductase Expression --- p.87 / Chapter CHAPTER 5 --- EVALUATION OF THE ROLE OF SIMVASTATIN IN INSULIN SECRETION VIA HMG CO A REDUCTASE REGULATION --- p.90 / Chapter 5.1 --- Effect of Simvastatin on Insulin Secretion --- p.90 / Chapter 5.2 --- Effect of Different Concentrations of Simvastatin on Insulin Secretion --- p.94 / Chapter 5.3 --- Effect of Simvastatin on Insulin Content --- p.96 / Chapter CHAPTER 6 --- ROLE OF AMPK EXPRESSION IN INSULIN SECRETION PATHWAY --- p.100 / Chapter 6.1 --- Effect of Simvastatin on Thr172 p-AMPK α and AMPK α1 Expressions --- p.100 / Chapter 6.2 --- Evaluation of the Role of Simvastatin in AMPK Regulation --- p.104 / Chapter 6.3 --- Evaluation of the Role of PP2A in AMPK Regulation --- p.108 / Chapter 6.4 --- Evaluation of the Role of Simvastatin on Insulin Secretion via AMPK Regulation --- p.111 / Chapter 6.4.1 --- AMPK Regulation on Releasable Insulin Secretion --- p.111 / Chapter 6.4.2 --- AMPK Regulation on Non-Releasable Insulin Content and Total Insulin Content --- p.112 / Chapter CHAPTER 7 --- EFFECT OF SIMVASTATIN ON THE EXPRESSION OF REGULATORY PROTEINS INVOLVED IN INSULIN SECRETION --- p.119 / Chapter 7.1 --- Effect of Simvastatin on SREBP-2 Expression --- p.119 / Chapter 7.2 --- Effect of Simvastatin on Caveolin-1 Expression --- p.121 / Chapter 7.3 --- Effect of Simvastatin on Calcium Sensing Receptor Expression --- p.123 / Chapter CHAPTER 8 --- EFFECT OF SIMVASTATIN-NA+ ON INSULIN SECRETION --- p.126 / Chapter 8.1 --- Effect of Simvastatin-Na+ on HMG CoA Reductase Expression --- p.126 / Chapter 8.2 --- Effect of Simvastatin-Na+ on Insulin Secretion --- p.128 / Chapter 8.3 --- Effect of Different Concentrations of Simvastatin-Na+ on Insulin Secretion --- p.130 / Chapter 8.4 --- Effect of Simvastatin-Na+ on Insulin Content --- p.132 / Chapter CHAPTER 9 --- EFFECT OF PRAVASTATIN ON INSULIN SECRETION --- p.136 / Chapter 9.1 --- Effect of Pravastatin on Insulin Secretion --- p.136 / Chapter 9.2 --- Effect of Pravastatin on Insulin Content --- p.138 / Chapter CHAPTER 10 --- EFFECT OF METHYL-B-CYCLODEXTRIN ON INSULIN SECRETION --- p.142 / Chapter 10.1 --- Effect of Methyl-β-cyclodextrin on Insulin Secretion --- p.142 / Chapter 10.2 --- Effect of Methyl-β-cyclodextrin on Insulin Content --- p.144 / Chapter CHAPTER 11 --- DISCUSSION --- p.149 / Chapter 11.1 --- Importance of Studying Porcine Pancreatic Islets and Islet Distribution --- p.150 / Chapter 11.2 --- Screening of Concentration and Incubation Time of Simvastatin on Porcine Pancreatic Islets --- p.152 / Chapter 11.3 --- Glucose-Independent Effect of Simvastatin on Protein Expression of HMG CoA Reductase --- p.154 / Chapter 11.4 --- Role of AMPK in HMG CoA Reductase-Modulated Insulin Secretion --- p.159 / Chapter 11.5 --- Role of SREBP-2 in Simvastatin-Modulated Regulation --- p.174 / Chapter 11.6 --- Role of Calcium Sensing Receptor in Simvastatin-Modulated Regulation --- p.175 / Chapter 11.7 --- Role of Caveolin-1 in Simvastatin-Modulated Regulation --- p.179 / Chapter 11.8 --- "Effects of Simvastatin-Na+, Pravastatin and Methyl-β-cyclodextrin, and Importance of Endoplasmic Reticulum in Insulin Secretion" --- p.183 / Chapter CHAPTER 12 --- CONCLUSIONS AND FURTHER STUDIES --- p.197 / Chapter 12.1 --- Conclusions --- p.197 / Chapter 12.2 --- Further Studies --- p.203 / REFERENCES --- p.207

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_327176
Date January 2010
ContributorsWong, Mei Fung., Chinese University of Hong Kong Graduate School. Division of Pharmacology.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xiii, 251 leaves : ill. (some col.) ; 30 cm.
RightsUse of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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