The Renin-Angiotensin System: Current Research Progress in The Pancreas (eBook)

Preface 7
Prologue 9
Prologue 10
Contents 11
Part I The Pancreas 15
1 Overview of the Pancreas 16
1.1 Structure of the Pancreas 16
1.2 Development of the Pancreas 19
1.3 Molecular Hierarchy of the Pancreatic Development 21
References 24
2 Physiology of the Pancreas 26
2.1 ExocrineEndocrine Axis 26
2.2 Pancreatic Acinar Cells 28
2.3 Pancreatic Duct Cells 30
2.4 Pancreatic Islet Cells 33
2.4.1 Beta-Cells 34
2.4.2 Alpha-Cells 36
2.4.3 Delta-Cells and PP-Cells 36
References 38
3 Common Pancreatic Disease 41
3.1 Pancreatitis 41
3.1.1 Etiology and Prognosis 41
3.1.2 Treatments 44
3.2 Cystic Fibrosis 45
3.2.1 Etiology and Prognosis 46
3.2.2 Treatments 47
3.3 Pancreatic Cancer 48
3.3.1 Etiology and Prognosis 48
3.3.2 Treatments 49
3.3.3 Alternative Approach Using Traditional Chinese Medicine 50
3.4 Diabetes Mellitus 55
3.4.1 Etiology and Prognosis 55
3.4.2 Treatments 58
References 60
Part II The Renin-Angiotensin System (RAS) 64
4 Circulating RAS 65
4.1 Definition of Circulating RAS 65
4.2 Angiotensinogen 68
4.3 Angiotensin-Generating Enzymes 69
4.4 Angiotensin and (Pro)renin Receptors 71
References 75
5 Local RAS 79
5.1 Definition of the Local RAS 79
5.2 Local RAS in Carotid Body 80
5.2.1 Expression and Function of Carotid Body RAS 81
5.2.2 Carotid Body RAS and Congestive Heart Failure 82
5.3 Local RAS in Liver 83
5.3.1 RAS and Liver Function 84
5.3.2 Interaction Between Hepatic RAS and Vitamin D in T2DM 85
5.4 Local RAS in Intestine 87
5.4.1 Expression and Function of an Enterocyte RAS 89
5.4.2 Enterocyte RAS and Diabetes Mellitus 91
5.4.3 ACE2-Angiotensin (1--7)-Mas Receptor Axis and Intestinal Glucose Uptake 92
References 94
6 Pancreatic RAS 98
6.1 Acinar Cell RAS 99
6.2 Ductal Cell RAS 102
6.3 Stellate Cell RAS 105
6.4 Islet Cell RAS 106
References 111
Part III Research Progress of the RAS in Pancreas 115
7 Basic Techniques for Pancreatic Research 116
7.1 Cell Models 116
7.2 Animal Models 118
7.2.1 Animal Models of T1DM 119
7.2.2 Animal Models of T2DM 119
7.2.3 Animal Models of Pancreatitis 121
7.2.4 Animal Models of Pancreatic Cancer 122
7.3 Islet and Acinar Cell Isolation 122
7.4 Islet Transplantation 124
7.4.1 Animal Models of Islet Transplantation 124
7.4.2 Recent Advances in Islet Transplantation 125
7.5 Expression and Functional Studies 127
7.5.1 Gene expression studies 128
7.5.2 Protein Expression Studies 128
7.5.3 Transfection 129
7.5.4 Functional Studies 131
References 132
8 Current Research of the RAS in Diabetes Mellitus 138
8.1 Basic Studies of the RAS in T2DM 139
8.1.1 RAS Blockade Studies in Animal Models of T2DM 139
8.1.2 RAS Blockade-Induced Protective Mechanism 141
8.2 Clinical Studies of the RAS in T2DM 142
8.2.1 Recent Clinical Trials on RAS Blockers 142
8.2.2 DREAM Trial and Its Implications 143
8.3 Current Research on the RAS-Vitamin D-T2DM Axis 144
8.3.1 Vitamin D and RAS in T2DM 144
8.3.2 Role of Vitamin D in Modulating Islet RAS Expression and Function 146
8.3.3 Expression of Islet RAS in VDR Knockout Mice 148
8.4 Current Research on the RAS-GLP1-T2DM Axis 151
8.4.1 Role of DPP-IV Inhibition in T2DM 152
8.4.2 Interaction of Islet RAS and GLP-1 152
8.4.3 Potential Role of Vitamin D in Modulating Islet RAS and GLP-1 153
References 155
9 Current Research Concerning the RAS in PancreaticStem Cells 161
9.1 Source of Pancreatic Stem Cells 161
9.2 Current Research on Pancreatic Stem Cells 164
9.3 Current Research of the RAS on Stem Cells 167
9.3.1 The RAS and ESCs 168
9.3.2 The RAS and MSCs 168
9.3.3 The Vascular RAS and Erythropoiesis 170
9.3.4 The RAS and Fetal Tissues 170
9.4 Current Research on the RAS in Pancreatic Stem Cells 171
9.4.1 Limitations and Future Directions 177
References 178
10 Current Research of the RAS in Pancreatitis and PancreaticCancer 184
10.1 Basic Studies of the RAS in Pancreatitis 184
10.1.1 Evidence of a Local RAS and Its Roles in Pancreatitis 185
10.1.2 Potential Mechanisms of RAS-Mediated Oxidative Stress and Blood Flow in Pancreatitis 185
10.1.3 The RAS and Cytokine-Mediated Systemic Inflammation in Pancreatitis 186
10.2 Current Research of the RAS on Pancreatitis In Vivo 187
10.2.1 Effects of RAS Blockade in Rat Model of Caerulein-Induced AP 187
10.2.2 Effects of RAS Blockade in Rat Model of Obstructive AP 189
10.3 Current Research of the RAS on Pancreatitis In Vitro 192
10.3.1 Effects of Angiotensin II on ERK and CREB-Mediated IL6 Expression 193
10.3.2 Potential Crosstalk Between Angiotensin II-Induced ROS-Mediated ERK and NF B 193
10.4 Current Research of the RAS in Pancreatic Cancer 196
10.4.1 Expression and Regulation of the RAS Components in Tumours 197
10.4.2 RAS Blockade and Pancreatic Cancers 198
References 199
Epilogue 205
Epilogue 206
Index 207