Glucose Homeostatis and the Pathogenesis of Diabetes Mellitus

Contributors

Preface

Chapter One. G Protein-Coupled Receptors as Regulators of Glucose Homeostasis and Therapeutic Targets for Diabetes Mellitus

Abstract

Abbreviations

1 Introduction

2 Regulation of Glucose Homeostasis by GPCRs in the Central Nervous System

3 Regulation of Glucose Homeostasis by GPCRs for Peptides from Endocrine Pancreas

4 Regulation of Insulin Secretion by GPCRs

5 Regulation of Incretin Secretion by GPCRs

6 Regulation of Glucose Homeostasis by Orphan GPCRs

7 Summary

Acknowledgments

References

Chapter Two. Regulation of Glucose Homeostasis by GLP-1

Abstract

List of Abbreviations

1 Introduction

2 GLP-1 Biosynthesis, Secretion, and Degradation

3 Insulinotropic and Growth Factor Properties of GLP-1

4 Molecular Basis of GLP-1 Receptor Activation

5 Control of Pancreatic β-Cell Insulin Secretion by GLP-1

6 Altered GLP-1 Action in a Rodent Model of Insulin Resistance

7 Glucoregulatory Properties of GLP-1 Mediated by the Nervous System

8 GLP-1 Receptor Agonists

9 DPP-IV Inhibitors

10 GLP-1-Based Strategies for the Treatment of T2DM

11 Improved Glucoregulation After Bariatric Surgery

12 Safety Considerations for GLP-1-Based Therapeutics

13 Conclusion

Acknowledgments

References

Chapter Three. Physiology and Therapeutics of the Free Fatty Acid Receptor GPR40

Abstract

Abbreviations

1 Introduction

2 Molecular Cloning and Tissue Distribution of GPR40

3 Physiology of GPR40

4 Pharmacology of GPR40

5 Pathophysiology of GPR40

6 Conclusions

Acknowledgments

References

Chapter Four. Targeting GPR119 for the Potential Treatment of Type 2 Diabetes Mellitus

Abstract

Abbreviations

1 Introduction

2 Molecular Cloning and Localization of GPR119

3 Physiology of GPR119

4 Pharmacology of GPR119

5 Conclusions

Acknowledgments

References

Chapter Five. Enhanced Skeletal Muscle for Effective Glucose Homeostasis

Abstract

1 Introduction

2 Skeletal Muscle and Glucose Homeostasis

3 Skeletal Muscle Formation

4 Myogenic Regulatory Factors

5 Postnatal Development of Skeletal Muscle

6 Myostatin and Skeletal Muscle Mass

7 Enhanced Muscle Growth for Preventing Diabetes

8 Concluding Remarks

Acknowledgments

References

Chapter Six. Factors Affecting Insulin-Regulated Hepatic Gene Expression

Abstract

Abbreviations

1 Introduction

2 Insulin Secretion, Its Signaling Pathways, and Its Regulated Hepatic Gene Expression

3 Effects of Hormone and Nutrient on Insulin-Regulated Hepatic Gene Expression

4 Drugs and Phytochemicals Affecting Hepatic Insulin Action

5 Perspectives and Future Directions

Acknowledgments

References

Chapter Seven. The Roles of Peroxisome Proliferator-Activated Receptors in the Metabolic Syndrome

Abstract

1 Introduction

2 Tissue Distribution of PPARs Suggests Key Role in Lipid and Glucose Metabolism

3 Prototypic Nuclear Receptor Domains of PPARs

4 PPAR Ligands (Endogenous and Synthetic) and Coregulators

5 Key Target Genes of PPARs Related to the Metabolic Syndrome

6 Lessons Learned from Clinical Use of TZD Class of Antidiabetic Drugs

7 New, Novel PPAR Ligands for Treatment of the Metabolic Syndrome

8 Summary

Acknowledgment

References

Chapter Eight. Free Fatty Acids and Skeletal Muscle Insulin Resistance

Abstract

1 Historic Overview of the Scientific Understanding of Insulin Resistance

2 Lipids and Skeletal Muscle Insulin Resistance

3 Saturated Versus Unsaturated FFAs and Insulin Resistance

4 Additional Insights Into Mechanisms Involved Into FFA-Induced Muscle Insulin Resistance

5 FFAs, Mitochondrial Function, and Insulin Resistance

6 Is FFA-Induced Insulin Resistance a Cellular Adaptation Process?

7 Clinical Perspectives and Therapeutic Implications

8 Conclusions

References

Chapter Nine. Adiponectin Signaling and Metabolic Syndrome

Abstract

1 Introduction

2 Metabolic Syndrome and the Limitation of Current Treatment

3 Adiponectin and Adiponectin Receptors

4 Adiponectin Signaling in Key Metabolic Cells/Tissues Related to Metabolic Syndrome

5 Summary

References

Chapter Ten. Regulation of Pancreatic Islet Beta-Cell Mass by Growth Factor and Hormone Signaling

Abstract

Abbreviations

1 Introduction

2 GH, PRL, and Their Receptor Signaling and Actions in Beta Cells

3 IGF-1 and Its Receptor Signaling and Actions in Beta Cells

4 GH–IGF-1 Signaling Cross Talk and Collaborative Roles in Regulation of Beta-Cell Mass

5 Concluding Remarks

Acknowledgments

References

Chapter Eleven. The Impact of Dietary Methionine Restriction on Biomarkers of Metabolic Health

Abstract

Abbreviations

1 Rationale for Study of Dietary Methionine Restriction

2 Origins of Dietary Methionine Restriction as an Experimental Approach to Increase Longevity

3 Anti-Inflammatory Responses to Dietary Methionine Restriction and Longevity

4 Effects of Dietary MR on Energy Intake and Adiposity

5 Effects of Dietary MR on Energy Expenditure

6 Effects of Dietary MR on Fuel Selection and Metabolic Flexibility

7 Effects of Dietary MR on Hepatic Lipid Metabolism: Transcriptional Mechanisms

8 Transcriptional Effects of Dietary MR on Adipose Tissue

9 Sensing of Dietary MR

10 Perspectives and Future Directions

Acknowledgments

References

Chapter Twelve. Carbohydrate Metabolism and Pathogenesis of Diabetes Mellitus in Dogs and Cats

Abstract

1 Introduction

2 The Dog

3 The Cat

References

Chapter Thirteen. Impaired Insulin Signaling and Mechanisms of Memory Loss

Abstract

Abbreviations

1 Introduction

2 Diabetes and Cognitive Deficits

3 Central Insulin Regulation

4 Insulin Resistance and Hallmarks of Neurodegeneration

5 Common Mediators of Insulin Resistance and Cognitive Dysfunction

6 Insulin Resistance and Hippocampal Dysfunction

7 Role of IGF in Cognitive Function

8 Animal Models of Insulin Signaling Deficits

9 Role of Antidiabetes Drugs in the Treatment of Cognitive Dysfunction

10 Summary

Acknowledgments

References

Chapter Fourteen. The Role of PPARδ Signaling in the Cardiovascular System

Abstract

1 Introduction

2 Expression of PPARδ in the Cardiovascular System

3 The Role of PPARδ in Regulating the Function of Endothelial Cells

4 The Roles of PPARδ in the Vascular Smooth Muscle Cells

5 The Role of PPARδ in Regulating Macrophage Function

6 The Role of PPARδ in Fibroblast Proliferation

7 Roles of PPARδ in Myocardial Oxidative Metabolism

8 Anti-inflammatory Effect of PPARδ in Cardiomyocytes

9 Conclusions and Perspectives

Acknowledgments

References

Index