Amylin: physiology and pharmacology

01 Serial Editors......Page 1
02 Contents......Page 2
03 Foreword......Page 8
04 Preface......Page 10
Discovery and Nomenclature......Page 11
Amylin and IAPP......Page 12
Amylin Gene......Page 14
Amyloid and Association with Diabetes......Page 16
A Corrupted Literature......Page 17
Pramlintide......Page 18
References......Page 19
Summary......Page 29
Amylin in the Gut......Page 30
Control of Secretion......Page 32
Differential Control of Amylin versus Insulin Secretion......Page 33
Assays......Page 34
Normal Subjects......Page 35
Amylin in Insulin Deficiency......Page 36
Amylin in Type 2 Diabetes Mellitus......Page 38
Amylin Concentrations in Other Conditions......Page 39
Mechanisms of Amylin Elimination......Page 40
Continuous intravenous infusions......Page 42
Pharmacokinetics in Humans......Page 46
References......Page 47
Summary......Page 56
Molecular and Biochemical Characterization......Page 57
RAMPs and Calcitonin Receptors......Page 59
Distribution of Amylin Receptor Components......Page 60
Other Properties of RAMP Proteins......Page 61
Brain Distribution......Page 63
Binding in Area Postrema......Page 65
Peripheral Binding......Page 66
Definition of Amylinomimetic Class......Page 67
Amylin Receptor Antagonists......Page 68
Use of Selective Ligands......Page 70
References......Page 71
Summary......Page 75
Overview of Reported Actions......Page 76
Prior Theories of Pathogenic and Physiological Roles......Page 78
Insulin Resistance......Page 79
Counterregulation during Hypoglycemia......Page 80
References......Page 81
Summary......Page 86
Magnitude of Effect......Page 87
Potency of Effect......Page 88
Effect of Disrupting Amylin Signaling......Page 89
Amylin/CCK Synergy......Page 90
Pharmacology of Effect......Page 92
Further Characterization of Effect......Page 93
Localization of Effect to Area Postrema......Page 94
Amylin and Ghrelin Secretion......Page 98
Effect of Amylin on Drinking Behavior......Page 99
References......Page 100
Summary......Page 106
Metabolic Significance of Control of Gastric Emptying......Page 107
Gastric Emptying in Diabetes......Page 108
Magnitude of Effect......Page 109
Potency of Effect......Page 111
Pharmacology......Page 113
Localization of Effect......Page 114
Effects on Postprandial Nutrient Profiles......Page 115
Hypoglycemic Override......Page 118
References......Page 123
Summary......Page 129
Background......Page 130
Localization of Amylinergic Inhibition of Gastric Acid Secretion......Page 131
Peripheral (Local) Gastric Acid Inhibitory Effect of Amylin......Page 133
Amylin Inhibition of Gastric Acid Secretion During Hypoglycemia......Page 134
Physiological Relevance of Amylin Gastroprotection......Page 135
Pancreatic Enzyme Secretion......Page 137
Effects of Amylin on Pancreatic Exocrine Secretion In Vivo......Page 138
Effects of Amylin in Ar42j Cells......Page 139
Effects of Amylin in Isolated Acinar Cells......Page 141
Physiological Implications of Modulating Enzyme Secretion......Page 143
Effects of Amylin on Gallbladder Contraction......Page 144
Effects of Amylin on Intestinal Glucose Transport......Page 147
References......Page 149
Summary......Page 157
Arginine-Stimulated Secretion in Anesthetized Rats......Page 160
Effects of Amylin on Glucagon Release from Isolated Preparations......Page 161
Isolated Perfused Rat Pancreas......Page 163
Isolated Islets......Page 164
Hypoglycemia-Stimulated Glucagon Secretion......Page 166
Selective Effect on Arginine-Stimulated versus Hypoglycemia-Stimulated Glucagon Secretion......Page 168
Effect of Pramlintide in Anesthetized Rats......Page 172
References......Page 173
Summary......Page 178
Background......Page 179
Isolated beta-Cells and beta-Cell-like Lines......Page 180
Isolated Pancreatic Islets......Page 182
Isolated Perfused Pancreas Preparations......Page 184
Whole Animals......Page 186
Amylin Antagonists......Page 187
Amylin Agonists......Page 188
Localization of Effects on Insulin Secretion......Page 190
References......Page 191
Summary......Page 198
Profiles......Page 199
Dependence upon Fasted/Fed State......Page 200
Pharmacology......Page 201
Role of Endogenous Amylin......Page 203
Profiles......Page 205
Relationship to Lactate and Glucagon......Page 206
Timing of Changes......Page 207
The Hyperlactemic Clamp......Page 208
Postprandial Glucose......Page 210
References......Page 211
Summary......Page 214
Formation, Breakdown, and Content......Page 215
Isolated Stripped Rat Soleus Muscle......Page 216
Pharmacology......Page 218
Interactions with Insulin in Isolated Skeletal Muscle......Page 219
Glycogen Phosphorylase......Page 221
Cyclic Amp in Muscle......Page 222
Glucose Efflux from Muscle......Page 223
Potencies for Amylin Effects in Muscle......Page 224
Transport of Glucose, 3-O-Methylglucose, and 2-Deoxyglucose......Page 226
References......Page 228
Summary......Page 234
Direct Effects of Amylin in Hepatocytes......Page 235
Cori Cycle-Independent Effects on Endogenous Glucose Production......Page 236
References......Page 238
Effects of Amylin in Isolated Adipocytes......Page 240
References......Page 243
Summary......Page 244
Effects of Amylin on Blood Pressure......Page 245
Kidney......Page 248
Cutaneous Vascular Beds......Page 249
Pharmacology of Vascular Effect......Page 250
Direct Inotropic Effects......Page 251
References......Page 253
Summary......Page 256
Amylin Binding in Kidney......Page 257
Effects on the Renin-Angiotensin-Aldosterone System......Page 258
Hypothesis Linking Excess Amylin Action to Hypertension......Page 259
Effects on Kidney Fluid and Electrolyte Excretion......Page 261
Potassium......Page 263
Acid/Base Status......Page 264
Effects on Kidney Development and Endothelial Integrity......Page 266
Effects on Subfornical Organ and Drinking Behavior......Page 267
References......Page 268
Effects at Calcitonin Receptors......Page 274
Effects on Calcium Concentrations......Page 276
Effects on Osteoclasts......Page 278
Effects on Osteoblasts......Page 280
Effects in Models of Diabetic Osteopenia......Page 281
References......Page 282
Summary......Page 286
Effects on Body Temperature......Page 287
Effects on Memory......Page 288
Effects on Pain......Page 289
References......Page 292
Summary......Page 294
Pharmacokinetics......Page 295
Tolerability......Page 296
Type 2 Diabetes......Page 297
Hypoglycemia in Type 1 Diabetes......Page 298
Summary of Hypoglycemic Risk......Page 299
Effects on Counterregulatory Responses......Page 300
Postprandial Glucose Profiles......Page 301
Fructosamine......Page 302
Hemoglobin A1c, Type 1 Diabetes......Page 303
Hemoglobin A1c, Type 2 Diabetes......Page 306
Body Weight, Type 1 Diabetes......Page 308
Body Weight, Type 2 Diabetes......Page 309
Gastric Emptying......Page 311
Glucose Variability......Page 313
Bone Markers......Page 314
Renin/Angiotensin/Aldosterone System......Page 315
References......Page 316
19 Index......Page 326
20 Contents of Previous Volumes......Page 334