The Pancreatic Beta Cell

Former EditorsContributorsPrefaceChapter One: Metabolic Regulation of Insulin SecretionAbstract

1 Introduction

2 Glucose Metabolism and Insulin Secretion

3 Fatty Acid Metabolism and Insulin Secretion

4 Amino Acid Metabolism and Insulin Secretion

5 Association of Nutrient Metabolism with Pancreatic β-Cell Dysfunction

6 Conclusions

Chapter Two: Proinsulin Entry and Transit Through the Endoplasmic Reticulum in Pancreatic Beta CellsAbstract

1 Overview of Insulin Biosynthesis in Pancreatic Beta Cells

2 Proinsulin Entry into the ER

3 Proinsulin Transit Through the ER

4 Conclusion and Perspective

Acknowledgments

Chapter Three: Metabolism–Secretion Coupling and Mitochondrial Calcium Activities in Clonal Pancreatic β-CellsAbstract

1 Introduction

2 The Importance of Mitochondria to β-Cell Function

3 Oxidative Metabolism of β-Cells

4 Mitochondrial Ca2 + and Energy Metabolism

5 Ca2 + Handling in β-Cells

Acknowledgments

Chapter Four: Metabolic Syndrome and Ionic Channels in Pancreatic Beta CellsAbstract

1 Introduction

2 A Rapid Fly on Metabolic Syndrome

3 Physiology of Pancreatic Islets in Glucose Homeostasis

4 Physiology and Pathophysiology of Ionic Channels

5 Concluding Remarks

Chapter Five: The Beta Cell ImmunopeptidomeAbstract

1 Introduction

2 Autoantigens in T1D

3 Antigen Processing

4 Identifying T Cell Epitopes in T1D

5 Peptide-Based Intervention and the Role of Small Molecules

6 Advances in Mass Spectrometry for the Identification of PTMs

7 Conclusions

Chapter Six: Autophagy and Pancreatic β-CellsAbstract

1 Introduction

2 Autophagy

3 Autophagy and Pancreatic β-Cell Homeostasis

4 Adaptive Autophagy in Pancreatic β-Cell

5 Autophagy and Diabetes

6 Modulation of Autophagy as Therapeutic Strategy

7 Conclusions and Future Directions

Acknowledgments

Chapter Seven: The Somatostatin Receptor in Human Pancreatic β-CellsAbstract

1 Introduction

2 SST in Pancreatic Islets

3 Regulation of SST Secretion from Pancreatic δ-Cells

4 Effects of Exogenous SST on Hormone Secretion from Pancreatic Islets

5 Cellular Mechanisms Underlying SST Inhibition of Pancreatic Hormone Secretion

6 SSTRs in Pancreatic Islet Cells

7 Physiological Role of SST Signaling in Pancreatic Islets

8 SST and δ-Cells in Diabetes Mellitus

9 Clinical Uses of SSTR Agonists and Pancreatic Islets

10 Conclusions and Future Directions

Acknowledgments

Chapter Eight: Modulation of the Pancreatic Islet-Stress Axis as a Novel Potential Therapeutic Target in Diabetes MellitusAbstract

1 Introduction

2 Factors and Conditions Predisposing to the Development of Diabetes Mellitus

3 Current Options and Concepts for the Prevention and Treatment of Diabetes Mellitus

4 Implication of the Pancreatic Islet-Stress Axis in Diabetes Mellitus: A Potential Target for Prevention and Therapy

5 Conclusions and Future Directions

Acknowledgments

Chapter Nine: Regenerative Medicine for Diabetes: Differentiation of Human Pluripotent Stem Cells into Functional β-Cells In Vitro and Their Proposed Journey to Clinical TranslationAbstract

1 Introduction

2 Diabetes and Its History

3 Differentiation Protocols for Human Pluripotent Stem Cells to β-Cells

4 hESC/hPSC-Derived Beta Islets-Based Cell Therapy for Diabetes

5 Conclusion

Chapter Ten: The Calcium-Sensing Receptor and β-Cell FunctionAbstract

1 Introduction

2 The Calcium-Sensing Receptor (CaSR)

3 Effects of CaSR on β-Cell Adhesion, Coupling, and Communication

4 Effects of the CaSR on Insulin Secretion

5 Effects of the CaSR on β-Cell Proliferation

6 The CaSR and Diabetes Mellitus

7 Conclusion

Acknowledgment

Chapter Eleven: Cellular Inhibitor of Apoptosis Protein-1 and Survival of Beta Cells Undergoing Endoplasmic Reticulum StressAbstract

1 Introduction

2 ER Stress in the Balance Between Cell Death and Survival

3 ER Stress and Lipotoxicity in Beta Cell Failure

4 Role of cIAP1 in Beta Cell Survival Under ER Stress

Acknowledgments

Chapter Twelve: β-Cell Responses to Nitric OxideAbstract

1 Introduction

2 Cytokine-Induced Damage

3 Mechanisms of Nitric Oxide-Induced β-Cell Death: Apoptosis or Necrosis?

4 Recovery from Nitric Oxide-Induced Damage

5 Conclusions

Chapter Thirteen: Activated Protein C and Its Potential Applications in Prevention of Islet β-Cell Damage and DiabetesAbstract

1 Introduction

2 Protein C and Activated Protein C

3 Pancreas and Pancreatic Islet β-Cell Function

4 APC and β-Cell Preservation in Diabetes

5 Conclusions

Chapter Fourteen: Zinc and Its Transporters, Pancreatic β-Cells, and Insulin MetabolismAbstract

1 Introduction

2 Zinc and Its Transporters in Insulin Synthesis and Secretion in Pancreatic β-Cells

3 Zinc Transporters and their Physiological Roles and Contributions to Insulin Metabolism and Glucose Homeostasis: Studies in Mouse Knockout Models of Zinc Transporters

4 Zinc and Its Transporters in the Development of Diabetes in Humans

5 Conclusions and Future Directions

Acknowledgments

Chapter Fifteen: The NOTCH Pathway in β-Cell Growth and DifferentiationAbstract

1 Introduction

2 Role of the NOTCH Pathway in Pancreas Development

3 Evidence for Reactivation of the NOTCH Pathway in Adult Pancreatic Cells

4 Effect of the NOTCH Pathway on Proliferation, Dedifferentiation, and Redifferentiation of Cultured Human β-Cell-Derived Cells

Acknowledgments

Chapter Sixteen: Roles of HNF1α and HNF4α in Pancreatic β-Cells: Lessons from a Monogenic Form of Diabetes (MODY)Abstract

1 Introduction

2 Clinical Features of HNF1α Diabetes (MODY3)

3 Functional Regulation of β-Cells by HNF1α

4 HNF1α Regulates β-Cell Growth

5 HNF4α Gene and Diabetes

6 Functional Role of HNF4α in β-Cells

7 Anks4b Is a Novel Target of HNF4α in β-Cells

8 Concluding Remarks

Acknowledgments

Chapter Seventeen: Role of the Mammalian Target of Rapamycin (mTOR) Complexes in Pancreatic β-Cell Mass RegulationAbstract

1 Introduction

2 Pancreatic β-Cell Mass

3 Structure of mTORC1/mTORC2 Complexes

4 Insulin and mTORC2 Signaling in Pancreatic β-Cells

5 Integration of Insulin, Energy, and Stress Signals by mTORC1

6 Conclusions and Future Directions

Index